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Review

Antimicrobial Lipids from Plants and Marine Organisms: An Overview of the Current State-of-the-Art and Future Prospects

1
Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal
2
Centre for Environmental and Marine Studies, CESAM, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal
3
Centre for Environmental and Marine Studies, CESAM, Department of Biology, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal
*
Authors to whom correspondence should be addressed.
Antibiotics 2020, 9(8), 441; https://doi.org/10.3390/antibiotics9080441
Submission received: 10 June 2020 / Revised: 17 July 2020 / Accepted: 22 July 2020 / Published: 24 July 2020
(This article belongs to the Special Issue Antimicrobial Lipids from Plants and Marine Organisms)

Abstract

:
In the actual post-antibiotic era, novel ways of rethinking antimicrobial research approaches are more urgent than ever. Natural compounds with antimicrobial activity such as fatty acids and monoacylglycerols have been investigated for decades. Additionally, the interest in other lipid classes as antimicrobial agents is rising. This review provides an overview on the research about plant and marine lipids with potential antimicrobial activity, the methods for obtaining and analyzing these compounds, with emphasis on lipidomics, and future perspectives for bioprospection and applications for antimicrobial lipids. Lipid extracts or lipids isolated from higher plants, algae or marine invertebrates are promising molecules to inactivate a wide spectrum of microorganisms. These lipids include a variety of chemical structures. Present and future challenges in the research of antimicrobial lipids from natural origin are related to the investment and optimization of the analytical workflow based on lipidomics tools, complementary to the bioassay-guided fractionation, to identify the active compound(s). Also, further work is needed regarding the study of their mechanism of action, the structure–activity relationship, the synergistic effect with conventional antibiotics, and the eventual development of resistance to lipids, which, as far as is known, is unlikely.

Graphical Abstract

1. Introduction

The consumption of antibiotics in the world population is alarming. In 2016, the top five World Health Organization (WHO)’s major antibiotic consuming countries were Brazil, Turkey, Iran, Russia, and France, by decreasing order [1]. In Brazil, more than 2000 metric tons of antibiotics were consumed annually, followed by ca. 1000 metric tons in Turkey and Iran [1].
Both misuse and overuse of antibiotics has led to the development of antimicrobial resistance (AMR) in microorganisms, which has been a global problem and a growing threat for many years. Antimicrobial resistant microbes are found in people, animals, food, and the environment (hospital or other health care facilities, water, soil and air). Because of AMR, several disease conditions are becoming harder to treat, as tuberculosis, pneumonia, blood poisoning, gonorrhea, and foodborne diseases [2]. AMR leads to higher medical costs, prolonged hospital stays, and increased mortality, causing an economic burden for health care systems. The major cause of AMR is mostly due to misuse of antibiotics.
A number of 700,000 deaths occur worldwide because of drug-resistant diseases [3]. Tuberculosis causes 1.8 million deaths per year, while multidrug-resistant (MDR) tuberculosis causes 250,000 deaths per year and is a global priority for research and development. Gram-negative bacteria can cause death in days because of the lack of treatment options. By 2050, it is foreseen that drug-resistant diseases could cause 10 million deaths each year [3]. In 2017, the WHO identified a priority list of highly antimicrobial-resistant pathogenic microorganisms, also known as superbugs, that have developed survival mechanisms to circumvent the action of last-line antimicrobials (isoniazid, rifampicin, fluoroquinolone, carbapenem, third-generation cephalosporin, or vancomycin) [4]. There are twelve bacteria that have critical and high priority for treatment discovery, besides Mycobacterium tuberculosis, the causing agent of tuberculosis, including the “ESKAPE” pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae [5]. Superbugs cause 33,000 deaths each year, in Europe, by antibiotic-resistant bacterial infections. Italy is the European country with one-third of all cases (11,000 deaths in total), followed by France (more than 5500 deaths) and Germany (with 2300 deaths) [6,7].
The world now lives the so-called “post-antibiotic era.” The current guidelines and recommendations from the WHO claim for an interconnected action and national action plans in a multisectoral and sustained “One Health” approach. This is aimed to tackle AMR and achieve the United Nations’ Sustainable Development Goals for 2030 toward humans, food and feed, plants and crops, environment, terrestrial and aquatic animals [8].
According to a recent WHO’s report, there are 252 antimicrobial agents in preclinical pipeline, being developed to treat WHO’s priority pathogens, but at very early stages of development [9]. Even so, very few target the most critical resistant Gram-negative bacteria, thus, they will generate little benefit over existing treatments [9]. As such, it appears that the future will come up with an increased need for new compounds with antimicrobial activity and combined therapeutic strategies, which can be effective against superbugs and bring revenue to the pharmaceutical industry. At the same time, several alternative approaches to conventional antibiotics have been extensively studied, not only to be used in the clinical field but also in animal health, control insect pest, protect agricultural crops, improve food safety, and water disinfection. Developing strategies include antimicrobial peptides (AMP), phage therapy, photodynamic antimicrobial chemotherapy (PACT), nanoparticles, probiotics, lysins, antibodies, quorum sensing inhibitors, and immunotherapeutic agents [5,10,11,12,13,14]. Combination therapy or multi-target approaches are being developed to hinder antibiotic resistance or to sensitize microorganisms to antibiotic action [15]. Another strategy to overcome AMR is the combination of conventional antibiotics with other molecules, as natural products and/or antimicrobials from natural sources, as plants and marine organisms, to enhance the antimicrobial effect against a wide range of pathogens.
Medicinal plants and marine organisms are natural sources of many antimicrobial compounds [14,16,17,18]. Plant components with antimicrobial activity include alkaloids, sulfur-containing compounds, diterpenes/terpenoids [19], fatty acids (FA) [20,21,22], some carbohydrates [23], steroidal glycosides, and phenolic compounds [24]. Both primary and secondary metabolites are “generally recognized as safe” (GRAS) substances and the chance of triggering antimicrobial resistance is low [25]. Simultaneously, marine organisms, mainly slow-moving or sessile, have developed adaptive defense mechanisms to protect themselves against pathogenic microorganisms. In some cases, marine organisms maintain associations with microbiota, being bacterial symbionts responsible by the synthesis of antimicrobial molecules [26,27].

1.1. Synergistic Effects between Natural Products and Antibiotics

Phytochemicals exert potential antimicrobial activities against both resistant and sensitive pathogenic microorganisms through distinct mechanisms of action. Additionally, some of them exert in vitro synergistic effects when combined with conventional antibiotics [19]. These natural products have intrinsic antibacterial, antiviral, antifungal, and antiparasitic activity, usually in higher concentrations than synthetic compounds, but they can be used to potentiate the effect of drugs. Synergistic effects have been observed by simultaneous administration of phytochemicals with antibiotics by increasing the effectiveness of oxacillin, tetracycline, nalidixic acid, ofloxacin, chloramphenicol, gentamicin, erythromycin, penicillin, ampicillin, kanamycin, and ciprofloxacin, primarily antibiotics from the group of inhibitors of cell wall synthesis and protein synthesis [25,28]. Likewise, the combination of phytochemical with antibiotics significantly reduced the values of their minimum inhibitory concentrations (MIC) [19].
On the other side, the effects of antimicrobial compounds from marine organisms in combination with conventional antibiotics have been poorly explored. Synergistic interactions were found in combination of long chain polyunsaturated FA (PUFA) with benzoyl peroxide to inhibit the growth of S. aureus [29]. This synergistic effect of FA suggests an increase in the cell membrane’s permeability, improving the penetration of the antimicrobial agent [29]. Fucoidan increased oral bacterial killing when combined with antibiotics [30]. Two AMP, tachycitin and a big defensin from the horseshoe crab Tachypleus tridentatus acted synergistically in antimicrobial activities [31]. Fucofuroeckol-A from the kelp Eisenia bicyclis reversed erythromycin and lincomycin resistance of Propionibacterium acnes and demonstrated a weak synergistic effect with both antibiotics [32]. Two marine oligosaccharides showed a synergistic effect with azithromycin against a wild-type strain of P. aeruginosa [33].

1.2. Antimicrobial Lipids

FA, monoacylglycerols (MAG), sterols and terpene derivatives have been the most studied antimicrobial lipid classes over the decades [20,21,22,34,35]. The efficiency of these lipids over a wide spectrum of microorganisms is linked to their chemical structure and is influenced by the pH of the medium. The structure-activity relationship between free FA (non-esterified) and bacteria is based on the chemical structure of the FA and depends on the acyl chain length, the stereochemistry, the degree of unsaturation, or on the esterified form of FA [20,21]. Short-chain FA (C6 or lower) are effective against Gram-negative bacteria (high concentration and pH-dependent); long-chain FA (C12 or higher) are effective against Gram-positive bacteria (low concentration and pH-dependent); methyl esters of FA (FAME) decrease bacterial activity; sucrose esters increase bacterial activity; cis-isomers are more active than trans-isomers; unsaturated ones increase the activity against Gram-negative bacteria [21]. FA and MAG are mostly effective against Gram-positive bacteria, quite possibly because of the complexity of the cell wall of Gram-negative bacteria, and the lower complexity and greater porosity of the Gram-positive bacterial wall, made up of several layers of peptidoglycan [36], which provides a degree of porosity to bacteria that allows the penetration of the antimicrobial agent into the cell [10]. In these bacteria, the absence of an outer membrane and the porous structure of the peptidoglycan cell wall allow the entry of antimicrobial molecules through the cell wall [37]. FA are amphipathic molecules with the hydrocarbon chain representing the hydrophobic part, while the carboxylic acid group is hydrophilic. This group can be polar or anionic in aqueous solution depending on the pH of the medium. However, antimicrobial inactivation studies with free FA isolated from biological matrices (plants or marine organisms) deserve greater attention in the near future, since FA with antimicrobial properties are sometimes identified as the most abundant compounds in the active extracts. However, when they are isolated, they do not exert any activity against the tested microorganisms.
FA have also shown antifungal activity and have the advantage of being non-toxic to the environment as conventional antifungals. Although they have a high degree of specificity, the probability of developing resistance in pathogenic fungi is low [35]. The most important target of antifungal FA is the cell membrane. They increase the fluidity of the membrane, leading to leakage of intracellular components and cell death. Other targets include protein synthesis that can be inhibited by myristic acid (14:0) analogues, FA metabolism and topoisomerase activity that can be inhibited by acetylenic FA, among others [35]. Some are FA produced by plants as a defense mechanism against fungal attack such as acetylenic FA. These FA have a triple bond (C≡C) and their putative mechanism of action is the inhibition of sphingolipid synthesis [38]. Fungi are more inhibited by acetylenic FA derivatives than by ethylenic FA derivatives (FA with double bonds) [21]. Cyclopropane FA, which have a cyclic structure, also revealed antifungal activity [35]. The synergism of antifungal drugs with antifungal FA increases the susceptibility to those drugs, potentiating and prolonging their effect [39].
The antifungal efficiency of free FA increases with the increase in the carbon chain length. FA with proven activity against several fungi, both yeast and mold species, include saturated (4:0 to 16:0) and unsaturated (4:1 to 22:5) ones, which increase the fungicidal activity because of their greater freedom of movement within the cell membrane [40]. Methylated FA, also known as branched FA, (6-Me 17:1 and 12-Me 14:0), several saturated and unsaturated oxylipins (12:0 to 18:3) having one to three hydroxyl (OH-) groups have shown antifungal activity as well [40]. Oxylipins are originated from oxidation of PUFA and include different types of oxygenated FA derivatives.
A strong synergistic effect was evidenced on the antimicrobial action of linoleic acid (18:2) and oleic acid (18:1) against S. aureus and Kocuria kristinae, formerly known as Micrococcus kristinae, and also, a strong synergistic effect between 18:2 and MAG [monolaurin, MAG(C12:0)], or monomyristin, [MAG(C14:0)] greater than the isolated effect of 18:2 [41]. The 10- and 14-carbon MAG were effective against Helicobacter pylori, but free FA 14:1 and linolenic acid (18:3) were the most effective against this bacterium [42]. MAG(C10:0) was effective against Neisseria ghonorroeae, MAG(C12:0) against S. aureus and FA 12:0 against methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA), as recently reviewed by Yoon et al. (2018) [21]. A great advantage of antimicrobial lipids is that they are difficult to trigger resistance mechanisms in microbes, as observed for pathogenic fungi, as mentioned above [35] and also for bacteria, since they can grow in culture medium in the presence of these lipids, in sublethal concentrations, for up to a year without developing resistance [43].
Despite the promising results, mostly performed with pure commercial compounds, it is necessary to get an insight on the bioactive lipid molecules from natural sources. In some cases, pure lipid compounds were obtained from plant or marine organism extracts after several fractionation and purification steps, for further analysis and identification. There are few research works that were able to isolate a single lipid compound or a class of lipids. Additionally, a complex task is to verify the structure-activity relationship that requires further studies. Electron microscopy techniques and model membrane systems are useful tools to understand the mode of action of lipids toward the microorganisms. This laborious work requires a concerted action from several scientific disciplines as well as many methodological and technological fields and specialized personnel.
Thus, the study of lipids as molecules with antimicrobial potential, may be enhanced in the short term, with the help of lipidomics as an emerging tool for the identification and characterization of lipids (Section 5). This will promote the accurate identification of bioactive compounds, the discovery of new lipids and, eventually, compounds that can be used in combination with existing drugs to aid therapy.
A summary of the actual state-of-the-art on antibiotic resistance and search for novel antimicrobials, as natural product-derived lipids, is illustrated in Figure 1.

1.3. Aim of the Study

This review aims to provide a critical overview on the research about plant and marine lipids with potential antimicrobial activity, the methods for obtaining and analyzing these compounds with emphasis on lipidomics, and future perspectives for bioprospecting and applying these antimicrobial lipids.

2. Antimicrobial Lipids from Plants

Over the evolution, higher plants have developed several resilience strategies that allow them to resist or escape external attacks (e.g., microorganisms, pathogens, and predators). Their innate immune system had to be equipped with highly complex mechanisms of resistance and survival. The defense mechanisms of plants are unique and consist of both physical barriers and production of secondary metabolites. Plant secondary metabolites are formed in particular biosynthetic pathways by means of substrate-specific enzymes. The precursors of these secondary metabolites stem from primary metabolites, such as amino acids, FA, sugars, or acetyl-CoA. Some of the secondary metabolites serve as constitutive chemical barriers against the microbial attack (phytoanticipins) while others serve as inducible antimicrobials (phytoalexins) [44].
Oxylipins are a large family of plants’ secondary metabolites derived from PUFA that make part of their immune system and play key roles as antimicrobial agents. They are formed through enzymatic or radical oxidation of FA 18:2 and 18:3, in order to protect plants against pests and pathogens [45]. The enzymatic biosynthesis of these molecules is triggered by an alpha-dioxygenase (DOX) and by lipoxygenases (LOX) [46,47] that lead to the formation of the different types of molecules, including hydroxy-, hydroperoxy-, divinyl-, oxo-, and keto-derivatives of FA. Oxylipins are formed during abiotic and biotic stresses [48]. They are plant signaling molecules that can induce cell death and have an effect on the growth of eukaryotic microbes [45]. A deeper knowledge on plant response to stresses at molecular, physiological and metabolic levels will allow the development of new plant-derived antimicrobial molecules for use in the clinical field and as biopesticides [48].
The search for novel antimicrobials has led to exploring also amide derivatives of FA because they are natural self-defense agents in plants. FA amides are bioactive lipids [49] formed by the amidation of long chain saturated and unsaturated FA (UFA) [50]. They have higher antimicrobial activity against yeasts and bacteria than unmodified FA [51]. Amide derivatives of FA possess a broad bioactivity against different pathologic conditions (bacterial and parasitic infections, cancer, inflammation, etc.,) and their mechanisms of action imply protein synthesis inhibition and membrane leakage [52]. Also, microorganisms inside healthy plant tissues are unique to explore novel bioactive compounds. The FA and their amides from plant’s endogenous microorganisms have been scarcely reported despite being bioactive in a variety of processes and should be more explored as new therapeutic agents [52].
Lipids represent up to 7% of the dry weight of the leaves of higher plants and are important constituents of cell membranes, chloroplasts, and mitochondria [53]. Besides their structural function as main constituents of cell membranes, they have functional roles in plants (intracellular mediators, extracellular signalers, inter-species communication, and plant defense) and also serve as energy reserves (namely in seeds during germination) [21]. Palmitic acid (16:0) is the major saturated FA in leaf lipids. On the other hand, chloroplast membranes can have up to 90% α-18:3 FA in some lamellae [21]. FA exist in plants mainly linked to more complex molecules, as acylglycerols, esterified to a glycerol backbone in the form of triacylglycerols, sterol esters, MAG and diacylglycerols, phospholipids, or glycolipids. Several lipid classes, besides FA and MAG, have been identified in a diverse group of higher plants and tested for their antimicrobial activity, as will be detailed in the next sub-sections. Figure 2 illustrates the chemical structures of the different lipid classes with antimicrobial activity isolated from natural sources.

2.1. Extraction and Isolation of Plant Lipids

Studies that extract or isolate lipids from plants to test their antimicrobial activity are scarce (Table 1). The biomass used to extract lipids includes leaves, fruits, seeds, stems, rhizomes, shoots, stem barks, and heartwoods (Table 1). Lipid extraction from plants is usually carried out with organic solvents of different polarities (mainly n-hexane, CHCl3, CH2Cl2, EtOAc, EtOH, BuOH, MeOH, and their mixtures) (Table 1). Liquid/liquid extractions or Soxhlet extraction are commonly performed to obtain total lipid extracts [54,55,56,57,58]. Instead of analyzing one lipid class or one lipid molecule, some studies have analyzed the total lipid extracts that were obtained by sequential extraction.
In order to obtain a class of lipids or a particular lipid, the total lipid extract can be fractionated into different groups of lipids, depending on the polarity of the compounds, by thin-layer chromatography (TLC) or by column chromatography. Thus, for example, to recover the neutral lipids (e.g., sterol esters and triacylglycerols) by column chromatography, the extract can be eluted with CHCl3, followed by acetone to elute the glycolipids and, finally, with MeOH to elute the phospholipids, as mentioned for the leaves, stems and fruit of Zygophyllum oxianum [59]. The majority of the studies on antimicrobial plant lipids obtained and analyzed FA and their derivatives. FA have been isolated from a series of plant parts by using MeOH/benzene/sulfuric acid, 85% ethanol or supercritical fluid extraction (SFE) with CO2 and analyzed as FAME [56,60,61,62,63,64].
Mixtures of FA and FAME were obtained, but it was not clear if these FA were found in the free or esterified forms, since the derivatization methods (methylation) used in these studies convert free and esterified FA to FAME. However, because of their high abundance, presumably, the referred FA were esterified to other lipids. Several oxylipins were retrieved from roots, stems, and leaves of Brazilian joyweed (Alternanthera brasiliana) by extracting with EtOH and EtOAc [65]. Acetylenic FA were isolated from the roots of Pentagonia gigantifolia with 95% ethanol [38].
Other lipid classes isolated from plants for antimicrobial testing include sterols and sterol derivatives, glyceroglycolipids, and sphingolipids (Figure 2 and Table 1). The first group includes free sterols, steryl glycosides, and acyl steryl glycosides. Free sterols have been extracted together with triterpenes from the seeds of date palm (Phoenix dactylifera) by using CHCl3 and acetone [66], from several parts of Withania somnifera, Euphorbia hirta, and Terminalia chebula with EtOAc [67] and leaves of candle bush (Senna alata) and rhizomes of fingerroot (Kaempferia pandurata) with EtOH [68]. β-sitosterol 3-O-β-D-glucopyranoside, a steryl glycoside, was obtained from the leaves of Sendudok (Melastoma malabathricum) with CHCl3/acetone/MeOH [69] and the acyl steryl glycosides sitosteryl 3-β-O-glucoside 6’-O-palmitate and stigmasteryl 3-β-O-glucoside 6’-O-palmitate were obtained from the roots of capotiraguá (Blutaparon portulacoides) with EtOH [70]. Glyceroglycolipids, namely sulfoquinovosyldiacylglycerols (SQDG) were retrieved from neem (Azadirachta indica) leaves by extracting with MeOH and separating by SiO2 column chromatography with CHCl3/MeOH [71] or extracted with petroleum ether and re-extracted with MeOH [72].
In the group of sphingolipids, different chemical structures were identified belonging to different subclasses: ceramides and glycosphingolipids, also known as cerebrosides (Figure 2 and Table 1). Artemceramide-B was identified from the roots of Artemisia incisa after extraction with MeOH and recovered by SiO2 column chromatography after elution of the extract with CH2Cl2/MeOH following previous elution with n-hexane/EtOAc [73]. A cerebroside (soya-cerebroside I), a sphingolipid glycoside (1-O-β-D-glucopyranosyl(2S,3S,4R,10E)-2-[(2’R)-2-hydroxytetracosanoylamino]-1,3,4-octadecanetriol-10-ene), and its aglycone form (2S,3S,4R,10E)-2-[(2’R)-2-hydroxytetra-cosanoylamino]-1,3,4-octadecanetriol-10-ene) were isolated from the stems of cucumber (Cucumis sativus) by CHCl3 fractionation of the methanolic extract [74]. New glycosphingolipids were isolated and characterized from the fruits of fiddle leaf fig (Ficus pandurata), panduramides A–D and newbouldiamide [75], and from the woods of the giant-leaved fig (Ficus lutea), 1-O-β-D-glucopyranosyl-(2S,3R,5E,12E)-2N-[(2′R)-hydroxyhexadecanoyl]-octadecasphinga-5,12-dienine, commonly named lutaoside [76]. All these compounds are inhibitors of microbial growth, except panduramides A–D and newbouldiamide that did not reveal any activity (Table 2).
The fractionation of the extracts has been usually carried out by column chromatography and the purification of the compounds can be achieved by semi-preparative HPLC.
Different analytical platforms have been used to identify and characterize the structure of lipids in plant extracts. Generally, in natural products research, several complementary methods are used, such as 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, gas chromatography (GC) coupled to a flame ionization detector (GC-FID) or to a mass spectrometer (GC-MS), as well as MS with electrospray ionization (ESI-MS). Liquid chromatography-MS (LC-MS) and LC-MS/MS has not been much used on antimicrobial plant lipids’ research, only for sphingolipids analysis [74] and for linoleate oxylipins’ structural characterization [65]. Besides these common techniques, two-dimensional NMR techniques (2-D NMR such as correlation spectroscopy-COSY, nuclear Overhauser effect spectroscopy-NOESY, heteronuclear single quantum coherence-HSQC, and heteronuclear multiple bond correlation-HMBC) have been used for the identification of artemceramide-D [73] and glyceroglycolipids [72]. Other methods are regularly used for the analysis of lipid extracts or their fractionation, such as TLC [57,69,74,77], column chromatography as mentioned above, or paper chromatography, but the information is very limited [69]. Analysis of FA is mostly performed by GC-FID or GC-MS, after derivatization. Total lipid extracts or lipid fractions are subjected to derivatization techniques using acid or alkaline hydrolysis or transmethylation to obtain FAME.
To identify and/or quantify mixtures of compounds, simpler techniques can be applied as biochemical assays using colorimetric tests, as for instance, for sterols’ and steryl glycosides’ identification and quantification [68,69,72]. The data obtained for compounds’ identification in these studies on antimicrobial plant lipids are normally compared with data reported in the literature, especially for spectroscopic data [72,83].

2.2. Susceptibility Testing, Inhibitory, and Microbicidal Activities of Plant Lipids

Several microbial strains were used in plant lipid studies, comprising Gram-positive bacteria, Gram-negative bacteria, acid-fast bacteria, yeasts, filamentous fungi, parasitic protozoa, and some MDR strains and/or hospital isolated strains, such as MRSA (Table 2).
The lowest MIC against S. aureus were observed for the mixture of lipid classes from the aerial parts of Hedyotis pilulifera (1.25 µg/mL) [83], the artemceramide-B from the roots of A. incisa (0.0313 mg/mL) [73], the linoleate oxylipins isolated from Alternanthera brasiliana (50 µg/mL) [65], and the FAME extracted from the shoots of Salicornia brachiata (60 µg/mL, the same MIC also verified for a MRSA strain) [61]. In the case of artemceramide-B, its high inhibitory potential against S. aureus was assigned to this polar lipid bearing four hydroxyl groups and an amide linkage between two long aliphatic chains [73]. In the case of the linoleate oxylipins from A. brasiliana plant tissues, five isolated oxylipins were also found to be synthesized by endophytic Bacillus strains isolated from this plant. So, it was speculated that the antimicrobial activity of the oxylipins from this plant could be derived from the endophytic bacteria, supposing an ecological crosstalk between this plant and its endogenous microbiome [65]. Also, the LC-MS/MS approach was crucial to identify these antimicrobial compounds both in the plants and in the bacteria, shedding some light on the plant–bacteria interplay [65].
The FA from the extract of Cassia tora’s leaves and stems exhibited MIC between 200 and 1000 μg/mL against MRSA [55]. The minimum bactericidal concentrations (MBC) against MRSA were determined on FAME from the leaves of Excoecaria agallocha (0.25 mg against S. aureus) [62], for MRSA the leaves of Sesuvium portulacastrum (1.0 mg/mL) [79], and the hexadecanoate methyl and hexadecanoic acid <n-> obtained from the stem bark of Scaphium macropodum (3.13 mg/mL against S. aureus) [82].
Other studies have tested the antimicrobial activity of lipids against other pathogenic microorganisms of great relevance for the clinical area and included in WHO’s guidelines, such as those of the “ESKAPE” group. The lipid extracts with greater inhibiting capacity over Escherichia coli were the FA and their derivatives from n-hexane and CHCl3 extracts of the heartwood of A. adianthifolia (1 µg) [79], and the acyl steryl glycosides obtained from roots of B. portulacoides (50 µg/mL) [70]. Also with low MIC values, the FAME extracted from the shoots of S. brachiata (0.5 mg/mL) [61] and the FAME and steroids from Trigonella foenum-graecum seeds (100 µg/mL) [63]. A MBC range between 1.0 and 2.0 mg/mL was verified for FAME extracts from the leaves of different plants [60,61,62].
Some lipid extracts were found to have low MIC against P. aeruginosa, as the FA and their derivatives obtained from the n-hexane and CHCl3 extracts of the heartwood of A. adianthifolia (50 µg) [79], FAME and steroids from fenugreek seeds (T. foenum-graecum, 100 µg/mL) [63], and the SQDG extracted from the neem leaves (A. indica, 128 µg/mL) [71]. MBC toward P. aeruginosa between 0.1 and 2.0 mg/mL were verified for the extracts of FAME from leaves of different plants [60,61,62], similarly to the findings for the E. coli strains.
For strains of Salmonella typhimurium, a high MIC value of 25 mg/mL was obtained from the stem bark extract of S. macropodum which contained four compounds including two FA (hexadecanoate methyl and hexadecanoic acid <n->) [82]. The SQDG extracted from the neem leaves showed antimicrobial activity against MDR strains of Salmonella typhi and Shigella dysenteriae, both with a MIC range between 32 and 64 µg/mL, and also against MDR strains of E. coli (64–128 µg/mL), P. aeruginosa (128 µg/mL), S. aureus (128–256 µg/mL), and K. pneumoniae (256 µg/mL) [71]. Also, identical MIC values (0.5 mg/mL) of FAME extracts [60,61,62] and FA [54] from different plants were observed against K. pneumoniae.
Studies with Mycobacterium sp. demonstrated antimicrobial activity of extracts of fenugreek seeds that contained a mixture of FAME and steroids, having a MIC of 100 µg/mL against M. tuberculosis [63]. Activity against Mycobacterium smegmatis was also verified by extracts containing hexadecanoate methyl and hexadecanoic acid <n-> FA from the stem bark of Malva nut, S. macropodum (3.13 mg/mL) and a MBC of 6.25 mg/mL [82]. Finally, the triterpenoids oleanolic acid and rotungenic acid were found to have activity against M. smegmatis with a MIC of 2.5 µg/mL and 1.25 µg/mL, respectively [83].
The fenugreek seed extracts from which conjugated linoleic acid methyl ester, saturated FAME, and steroids were identified, showed an inhibitory effect against Plasmodium falciparum with a MIC of 0.29 µg/mL [63].
The glycolipid SQDG isolated from neem has a broad-spectrum of activity against MDR bacterial strains [71] and anti-helminthic activity [72], which proves to be a promising natural antimicrobial agent. This class of compounds isolated from neem has demonstrated antiviral activity (herpes simplex viruses, HSV-1 and HSV-2) [71], significant DNA binding properties [84], and anti-leukemic activity [85]. However, it is difficult to isolate a single compound or a class of compounds from complex matrices as plants. In most studies, the antimicrobial effects may be due to a synergistic effect between several natural antimicrobial compounds, and not just to the referred lipids. As such, more studies must be done to understand which lipids can effectively be responsible by the inhibitory or microbicidal effect and the structure–activity relationship.

3. Antimicrobial Lipids from Marine Organisms

The most studied antimicrobial compounds of marine origin are peptides and alkaloids [86,87,88], contrarily to lipids. However, lipids are ubiquitously distributed in the different marine phyla, being quite abundant in some of them. Besides, several lipid classes from marine organisms have been recognized by their biological activity with a high potential to discover new antimicrobial compounds.

3.1. Marine Algae

Algal biomass is mainly composed by minerals, sugars, proteins, and lipids, that represent 1–15%, depending on the algal species and its habitat. Lipids found in the macroalgae from the three phyla, Rhodophyta, Chlorophyta, and Ochrophyta (Table 3), have demonstrated antimicrobial activity against Gram-positive and Gram-negative bacteria, yeasts, and fungi [29,89,90,91,92] (Table 4). Most of these antimicrobial lipids were isolated from Rhodophyta and Chlorophyta. While the former shows a high diversity of algal species as source of antimicrobial lipids, studies in Chlorophyta were focused on species belonging to the order Bryopsidales.
Several studies have tested the antimicrobial activity of macroalgal extracts obtained with different solvents. Shanab (2007) compared extracts from three macroalgae species (Sargassum dentifolium, Laurencia papillosa, and Jania corniculata) using two solvents, EtOH and CH2Cl2 [93]. Both extracts exhibited similar antimicrobial activity against all microorganisms tested (bacteria and yeasts), except against the mold Aspergillus flavus [93]. Several extracts from Gracilaria gracilis were studied to identify potential bioactive compounds [94]. CHCl3 and Et2O extracts (apolar solvents) presented lower extraction yields (% of dry algal biomass) than extracts from more polar solvents (EtOH, MeOH, and acetone). Less polar solvents isolated minor lipid classes (e.g., neutral and medium polar lipids) and showed lower amounts of soluble carbohydrates and total phenols than polar solvents. However, the diameter of the inhibition zones against B. subtilis were slightly lower in these extracts than in the extracts obtained with polar solvents (rich in soluble carbohydrates and phenolic compounds) [94]. These results suggest that although less polar solvents have lower yields, they contain compounds with interesting antibacterial features.
The lipids or lipid mixtures, their extracting solvent(s), and the methods used for their characterization in algae species are summarized in Table 3. The results of the antimicrobial assays with lipids and lipid-rich extracts from these algae are summarized in Table 4. Chemical structures of lipids isolated from algae are represented in Figure 2.

3.1.1. Fatty Acids

FA have been commonly reported in algae as antimicrobial agents. However, most studies tested total extracts instead of lipid-rich fractions and the antimicrobial activity was usually assigned to the most abundant FA in the extract [96,105,116]. The lack of target analyses limits the interpretation of the findings because FA are usually low abundant in total lipid extracts in the free form, being mainly esterified to other lipids, such as polar lipids, sterols, and triacylglycerols.
The antibacterial activity of the extracts from the microalga Dunaliella salina was suggested to be dependent on the presence of palmitic (16:0), 9,12,15-octadecatrienoic (α-linolenic, 18:3 n-3) and 18:1 n-9 together with volatile compounds [123]. The antimicrobial activity of the red macroalgae, J. corniculata, and L. papillosa, was ascribed to the presence of saturated [14:0, 16:0, stearic (18:0) acids] and the UFA [palmitoleic (16:1), 18:1 and nervonic (24:1) acids] [93]. Also, the antimicrobial activity of S. dentifolium was associated with the high relative abundance of 18:0, nonadecanoic (19:0), arachidic (20:0), petroselinic (18:1 n-12), and 24:1 acids [93]. Plaza et al. (2010) associated the antimicrobial and antifungal activities of the alga Himanthalia elongata and the microalga Synechocystis sp. with the high amount of 16:1 n-7 and 18:1 acids in the extracts, respectively [116]. The FA 18:3 was identified as an antibacterial agent in Chaetomorpha linum against Vibrio ordalii and V. vulnificus [99]. A relationship was found among the antimicrobial activity against S. aureus, E. coli, and C. albicans, and the FA docosapentaenoic (DPA, 22:5) and triacylglycerol contents [121]. In the green macroalga Ulva rigida, purified fractions of crude extracts with the highest antibacterial activity against S. aureus and Enterococcus faecalis comprised mainly 16:0, 18:1, and 16:1 n-7 FA [27]. Nevertheless, most of these studies neither isolated the predominant FA nor tested its activity. The FA 16:0 was the most abundant FA in Gracilariopsis longissima’s lipid extracts, that presented antibacterial activity against several Vibrio species. However, the pure FA 16:0 did not show any antibacterial activity [108]. On the other hand, some studies have isolated, purified, and characterized the FA with potential antimicrobial activity. For instance, marine diatoms revealed to be a rich source of FA with antibacterial properties. Studies with the diatom Navicula delognei allowed the isolation and identification of two FA (6Z,9Z,12Z,15Z)-hexadecatetraenoic acid (16:4 n-1) and (6Z,9Z,12Z,15Z)-octadecatetraenoic acid (18:4 n-3) and an ester (E)-phytol(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate with potent antibacterial effect against S. typhimurium, S. aureus, and S. epidermidis [124]. Two FA with antibacterial features were isolated from the marine diatom Phaeodactylum tricornutum, (9Z)-hexadecenoic acid (16:1 n-7), and (6Z,9Z,12Z)-hexadecatrienoic acid (HTA, 16:3 n-4) [125]. Both FA inhibited the growth of S. aureus and S. epidermidis [125]. Furthermore, 16:1 n-7 showed a potent antibacterial activity against two MRSA strains, and HTA against the Gram-negative marine bacterium Listonella anguillarum [125]. From the same diatom species, the eicosapentaenoic acid (EPA, 20:5 n-3) was isolated and tested, inhibiting the growth of Gram-negative and Gram-positive bacterial species, including MRSA [126]. The presence of double bonds in C16 FA was suggested to be crucial for their antibacterial action [125]. A higher (two-fold) inhibitory effect against S. aureus was recorded for 16:1 n-7 in relation to HTA isolated from the marine diatom P. tricornutum [125]. Nevertheless, in the macroalga Sargassum pallidum, free FA fractions having higher proportion of UFA demonstrated to be more active against more microorganisms like S. aureus, C. albicans, A. niger, and Septoria glycines [118]. Five UFA ethyl esters were isolated from the red macroalga Laurencia okamurai: (9Z,12Z,15Z,18Z,21Z)-ethyl tetracosa-9,12,15,18,21-pentaenoate, (10Z,13Z)-ethyl nonadeca-10,13-dienoate, (9Z,12Z)-ethyl nonadeca-9,12-dienoate, (Z)-ethyl octadec-13-enoate, and (Z)-ethyl hexadec-11-enoate [109]. All FA ethyl esters revealed individual antifungal activity against Candida glabrata, four of them against Cryptococcus neoformans and two against Trichophyton rubrum [109].
Although several studies have suggested that the FA chain length and double bond position influence their antimicrobial activity, there is no unanimity on the correlation between PUFA and antimicrobial activity [127].

3.1.2. Glycolipids

Glycolipids are the predominant lipids in the chloroplasts’ membranes of plants, eukaryotic algae, and cyanobacteria. They are recognized by their essential role in photosynthesis and by their structural functions as major components of the thylakoid membranes [128,129]. Algae synthesize two major types of glycolipids: neutral galactolipids and negatively charged sulfolipids. Neutral galactolipids include monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), and their lyso forms [monogalactosylmonoacylglycerol (MGMG), and digalactosylmonoacylglycerol (DGMG)]. Sulfolipids include SQDG and its lyso form sulfoquinovosylmonoacylglycerol (SQMG).
Glycolipids have been identified as biogenic compounds possessing a variety of bioactivities, such as antioxidant, antiviral, or antitumor [89,95,103,122,130,131,132]. The biological activity of glycolipids has been associated to the length of their fatty acyl chains, the number and position of the double bonds, the structure of the sugar moiety, and its anomeric configuration [131]. Gerasimenko et al. (2014) characterized the FA profiles and the antimicrobial activity of glycolipid fractions from S. pallidum throughout the year but could not assign any relationship between the amount of UFA and antimicrobial activity of DGDG, MGDG, and SGDG fractions [118]. However, a dependent effect of SFA level was observed in the antimicrobial activity of SQDG and MGDG fractions [118].
Several studies identified glycolipid fractions from algae having antimicrobial activity [89,103], even though only a few could isolate and characterize the main molecular species responsible for this activity. SQDG(20:5/16:0) was isolated from the red macroalga Gigartina tenella, which inhibited HIV-1 reverse transcriptase [107]. The sulfolipid 1-O-palmitoyl-3-O(6′-sulfo-α-quinovopyranosyl) glycerol (SQMG 16:0) was isolated from the methanolic extract of the brown seaweed Sargassum wightii and its activity was tested against Xanthomonas oryzae pv. oryzae [120]. The sulfolipid (2S)-1,2-di-O-palmitoyl-3-O-(6′-sulfo-α-D-quinovopyranosyl) glycerol, SDGQ(16:0/16:0), from the green alga Caulerpa racemosa was found to be a potent anti-HSV-2 agent [95]. An enriched sulfolipid fraction obtained from the red macroalga Osmundaria obtusiloba demonstrated potent antiviral activity against the herpes viruses HSV-1 and HSV-2, being the SQDG(14:0/16:0) the most abundant molecular species identified in that fraction [111]. However, that sulfolipid-rich fraction had a lower antiviral activity than the crude MeOH fraction, maybe due to synergistic effects with other glycolipid species, such as MGDG and DGDG [97,111]. SQDG (14:0/16:0) was identified in the glycolipid-rich extracts from the brown seaweed Sargassum vulgare as the main responsible for their anti-HSV-1 and anti-HSV-2 activity [119]. Promising results were recorded in the antibacterial activity of the glycolipid-rich fraction from the brown macroalga Fucus evanescens against P. acnes, MGDG (18:3/18:3) being the main active compound [115]. The authors synthesized this glycolipid and replicated the bioassay, but its inhibition efficiency toward P. acnes was lower (50%) than the glycolipid-rich fraction (>99%) [115], suggesting a synergistic antibacterial effect with other glycolipid compounds. Additionally, the antiviral activity of SQDG and SQMG isolated from Ulva fasciata, Laurencia papillosa, Galaxoura cylindrica, Dictyota fasciola, and Taonia atomaria was shown against HSV-1. This activity was attributed to the high concentration in these glycolipids [89]. The sulfolipid fraction also demonstrated a high inhibition against E. coli and B. subtilis, being the extracts from U. fasciata and T. atomaria those with the highest inhibitory capacity [89]. The potent antiviral effect of sulfolipids has been related with the negative charge of their sulfonate group as verified for marine polysaccharides [133].
Glycolipids from the red alga Chondria armata were recognized by their antibacterial and antifungal activities against several pathogens, such as C. albicans and C. neoformans or Klebsiella sp. [104]. The main bioactive lipid from the glycolipid fraction was identified as 1-eicosapentanoyl-2-palmitoyl-3-O-galactopyranosyl-glycerol, MGDG(20:5/16:0) [104]. The isolated fractions of MGDG and SQDG obtained from the lipophilic fractions of the brown seaweed Laminaria cichorioides inhibited the growth of the yeast Safale and C. albicans, the fungi A. niger and F. oxysporum, and the bacteria S. aureus and E. coli [91].
Several studies demonstrated higher antimicrobial activity in lipid-rich fractions than in total lipid extracts [91,118]. In the brown seaweed S. pallidum, the isolated fractions of glycolipids and free FA demonstrated to be more efficient in inhibiting bacterial growth than the total lipid extract [118]. The antimicrobial activity efficiency may be conditioned by seasonal variation, that must be related with shifts in the lipid profiles promoted by alterations in growth-related environmental conditions [118]. Nevertheless, a seasonal variation was not always verified, like in the green seaweed U. rigida that demonstrated a uniform antimicrobial activity throughout the year [27].

3.1.3. Other Lipids

The exploration of algal lipidomes has revealed a panoply of compounds with antimicrobial activity. Two compounds with antiviral properties against Semeliki forest and Japanese encephalitis viruses were isolated from U. fasciata’s lipophilic fractions, a sphingosine (N-palmitoyl-2-amino-1,3,4,5-tetrahydroxyoctadecane) and a ceramide (erythro-sphinga-4,8-dienine-N-palmitate), respectively [101,102]. Two bromoditerpenes, with antibacterial and antimalarial activity against S. aureus and the chloroquine-resistant P. falciparum, respectively, were isolated from the red alga Sphaerococcus coronopifolius [114]. Four halogenated sesquiterpenes isolated from the surface of the red macroalga Laurencia spp. demonstrated antibacterial activities toward six Gram-negative bacteria such as V. parahaemolyticus, Chromobacterium violaceum, or Erwinia sp. Neophytadiene and phytol were identified in the microalga D. salina as putative antimicrobial compounds against E. coli, S. aureus, C. albicans, and A. niger [123]. Several terpenes isolated from the brown seaweeds Sargassum fusiforme and S. vulgare were identified as putative antimicrobial molecules against clinical bacteria [117]. Terpenes were also suggested as antibacterial compounds against MRSA and E. coli in the red seaweeds Caulerpa racemosa and Caulerpa lentillifera [96].
Clerosterol was the main compound identified in a bioactive fraction from the green seaweed Codium amplivesiculatum against Gram-positive (S. aureus) and Gram-negative (V. parahaemolyticus) bacteria [100]. However, this compound did not display antibacterial activity when tested alone [100]. Different phospholipid classes, such as phosphatidylethanolamine and phosphatidylserine were identified in the red seaweed Pyropia orbicularis, as putative antimicrobial compounds, together with MGDG [113].

3.1.4. Photosynthetic Pigments

Pigments are not recognized as lipids, but they are present in the total lipid extracts of algae since they are extracted from the biomass along with lipids. Besides, in most studies, they were not removed from the lipid extracts. Pigments are mainly recognized by their antioxidant activity [134,135], but some studies have attributed a weak antibacterial activity to photosynthetic pigments such as chlorophylls and carotenoids [93]. Pheophytin α and chlorophyllide α from the microalga Isochrysis galbana were found to have a high antibacterial activity against marine strains of Brevibacterium and Micrococcus [136]. Carotenoid derivatives (β-cyclocitral and α- and β-ionone) from the microalga D. salina extracts were suggested to be responsible for its antimicrobial activity [123]. Fucoxanthin-rich fractions from the brown macroalga L. cichorioides demonstrated weak activity against yeast (Safale and C. albicans) and bacteria (S. aureus and E. coli), while chlorophyll fractions showed antibacterial activity against S. aureus and E. coli [91]. Photosynthetic pigments isolated from the brown macroalga S. pallidum’s extracts presented antifungal and antibacterial activities, chlorophylls (chlorophyll α as the main component) being the mediator to inhibit the growth of the fungi S. glycines and A. niger, while fucoxanthin was effective against E. coli [118].

3.2. Marine Invertebrates

The chemotaxonomic diversity of marine invertebrates is responsible for the large number of novel compounds identified in their phyla. Tropical biodiversity-rich benthic communities have been the most explored, thus the most fruitful in the identification of new potential antimicrobial compounds [137,138,139]. However, less conventional environments such as the Arctic ocean or mesopelagic communities have been started to be surveyed [140,141].
Marine invertebrates comprise a growing source of natural compounds, showing novel structures for biomedical and health-promoting applications [142]. Bioprospection of new compounds from marine invertebrates has revealed to be a prolific work to discover diverse bioactive compounds with action toward a broad spectrum of microorganisms [140,143]. Some of these reports have identified total lipid extracts as a potential source of bioactive compounds, lacking a sequential workflow of isolation, characterization, and purification of the metabolites responsible for the activity [99,143]. Although most of these studies used classical bioprospection methods to identify the bioactive compounds from marine species, others followed eco-friendly approaches by using fishing waste [141] or seafood by-products [144].
Phyla of marine invertebrates recognized as sources of antimicrobial compounds [16,145] include porifera [146,147], crustacean [148,149], mollusk [144,150,151], or cnidaria [137,139]. Some bacteria isolated from marine organisms have also disclosed antibacterial activity, such as Actinobacteria from sponges [26].
The main antibacterial natural products identified in marine invertebrates were peptides, polyketides, alkaloids, terpenes, and lipopeptides [14,34,150,152]. However, several antimicrobial lipids classes have been identified. Marine invertebrates produce an array of unique lipids originating from unusual biosynthetic pathways that are not common in other environments, as a result of thriving in diverse and extreme environments [142,153].
Porifera represents the most studied phylum of marine invertebrates for antimicrobial compounds’ bioprospection, including lipids [154,155]. The high contribution of these ancestral metazoans for bioactive compounds’ research seems to be related to their high filtering activity, pumping water during feeding, which expose them to viruses, bacteria, and eukaryotic organisms (pathogenic and non-pathogenic) [156,157].
Table 5 assembles the information regarding lipids from marine invertebrate species having antimicrobial activity. Table 6 summarizes the information about the antimicrobial properties, the tested organisms, and the antimicrobial assays for each marine invertebrates’ species listed in Table 5. Figure 2 illustrates the chemical structure of the main lipid classes with antimicrobial properties from these natural sources.

3.2.1. Fatty Acids

FA identified in marine invertebrates display a high diversity of chemical structures that are scarce or inexistent in other environments, such as very long chain PUFA or cyclic forms [158,159,160]. A C14 acetylenic FA isolated from the sponge Oceanapia sp. revealed antimicrobial activity against nine microbial strains, including yeasts and the bacteria E. coli, P. aeruginosa, B. subtilis, and S. aureus [161]. Complex FA mixtures containing very long chain FA were isolated from the sponge Agelas oroides and tested as anti-infectious agents [162]. These FA inhibited the enoyl reductases, enzymes that catalyze the last step of the elongation cycle in FA synthesis, in P. falciparum, M. tuberculosis,, and E. coli [162]. An acetylenic FA having antibacterial activity against S. aureus and E. coli was discovered in the marine sponge Paragrantia cf. waguensis [163]. Ravichandran et al. (2010) suggested 18:1 and 18:2 FA as antimicrobial compounds from the hemolymph and hemocytes of brachyuran crabs with greatest activity against V. cholerae, S. flexneri, S. pyogenes, and E. coli [148]. Brominated FA from a sponge of the genus Xestospongia showed antimicrobial activity against MRSA, S. mutans, and S. sobrinus [138]. Anti-infective brominated long-chain acids, termed motualevic acids, and an enantiomer of antazirine, were isolated from the sponge Siliquariaspongia sp. with activity against S. aureus and MRSA [164]. A recent study screening mesopelagic species as a source of potential antimicrobial compounds recognized the extracts of the lanternfish Myctophum punctatum and the Mediterranean krill Meganyctiphanes norvegica to inhibit the growth of MRSA, MSSA, and M. tuberculosis [141]. Extracts of both marine species were fractionated, and their composition was elucidated by LC-UV analysis. EPA, 4,7,10,13,16,19-docosahexaenoate (DHA, 22:6 n-3) and 8,11,14,17-eicosatetraenoic (ETA, 20:4 n-3) acids were the most abundant components in the lipid fractions of both marine species [141]. The 14-methyl-5,9-pentadecadienoic FA from the phospholipid pool was isolated and identified in the gorgonian coral Eunicea succinea and it was active against S. aureus and E. faecalis [137]. Quantitative data on antimicrobial efficiency are shown in Table 6.

3.2.2. Sterols

Sterols with singular structures were isolated from marine invertebrates, exhibiting novel carbon skeletons. Marine sponges were found to be sources of steroid sulfates with antiviral activity against HIV [165,166] and against feline leukemia virus (FeLV) [166] and antifungal activity against the yeasts C. albicans [167,168] and S. cerevisiae [168,169]. Three sterols were isolated and identified in the marine sponge Haliclona simulans with anti-mycobacterial and anti-trypanosomal activity [170]. The EtOAc extract of the flesh of the rock oyster Saccostrea glomerate was fractionated, and the best active fraction showed several sterols (e.g., cholesterol, stigmasterol, sitosterol) and FA as putative active compounds with antibacterial and antifungal activities against a broad spectrum of microorganisms [171]. Steroidal glycosides (e.g., eryloside, wondosterols, sarasinoside, sokodosides) isolated from marine sponges also showed antimicrobial properties [172,173,174,175].

3.2.3. Polar Lipids

Polar lipids are the main constituents of biological membranes and are also present in biofluids. The methanolic extracts of both the hemolymph (plasma) and hemocytes (plasma cells) of six brachyuran crabs revealed antimicrobial activity against sixteen bacterial and fungal pathogenic strains [148]. The antimicrobial activity of the hemolymph extracts was assigned to the presence of polar lipids [148].
A new family of antimicrobial glycolipids, caminosides, isolated from the marine sponge Caminus sphaeroconia showed a potent in vitro inhibition against a panel of human and plant pathogens (e.g., MRSA, vancomycin-resistant Enterococcus) and enteropathogenic E. coli (EPEC) [147,176]. Several ceramide and glycolipid molecular species have been isolated from soft corals of the genus Sinularia, and exhibited antibacterial and antifungal activity against seven microbial strains [139]. A ceramide from the cnidaria Lobophytum crassum showed moderate antibacterial activity against P. aeruginosa, S. epidermis, B. subtilis, and S. aureus [177].
Six lysophospholipids (lyso-platelet-activating factor, PAF) isolated from the sponge Spheciospongia purpurea displayed moderate antifungal activity against C. neoformans, C. glabrata, T. rubrum, and A. fumigatus [146]. The lyso-PAF molecular species were identified as PAF(16:0), PAF (16:1 n-5), PAF (18:0), PAF (18:1 n-7), PAF (18:1 n-11), and PAF (18:1 n-13) [146]. Two lyso-PAF, 1-O-hexadecyl-sn-glycero-3-phosphocholine and 1-O-octa-decyl-sn-glycero-3-phosphocholine, from the demosponge Suberites domuncula were separated and purified by reverse-phase (RP) HPLC, with further characterization by FIA-MS, LC-MS, and ESI-MS [157]. These compounds demonstrated a potent antibacterial activity against the bacterium SB1, isolated from S. domuncula, which presented a high species-level similarity (>98%) to the α-Proteobacterium MBIC3368 [157].

3.2.4. Other Lipids

Diverse structural modifications of isoprene units provide terpenes with a large range of biological activities [34]. These compounds were isolated mainly from Demospongiae species [178,179,180,181,182] and displayed antimicrobial activity against several infectious agents [183,184,185,186]. Six sesquiterpenoids, termed halichonadins, isolated from the marine sponge Halichondria sp. showed antimicrobial activity against the bacterium M. luteus, the yeast C. neoformans, and the mold Trichophyton mentagrophytes [187,188]. A cembranoid diterpene isolated from the cnidaria L. crassum showed strong antibacterial activity against P. aeruginosa, S. epidermis, B. subtilis, and S. aureus [177]. Two meroterpenoids, rossinones, from the Antarctic ascidian Aplidium sp. exhibited antiviral, antibacterial, and antifungal activities [189].
Terpenes with functional activities were identified in the cnidaria phylum, as from the soft coral Antillogorgia elisabethae [192]. Seven diterpenes showed potent antibacterial activity against the Gram-positive bacteria S. pyogenes, S. aureus, and E. faecalis [192]. A new series of lipids, termed mololipids, were found in the lipidome of a sponge from the order Verongida (recognized as “the Moloka’i sponge”) and were reported to be active against HIV-1 [191]. These lipids present a core moloka’iamine nucleus with two FA-derived side chains, saturated linear and iso-methyl branched ranging from 14 to 20 carbons [191].

3.2.5. Pigments

Xanthophyll, β-cryptoxanthin, and β-carotene obtained from the flesh and coelomic fluid of Holothuria scabra (sea cucumbers) showed antibacterial activity against S. aureus [193]. Skin pigments of the jumbo squid Dosidicus gigas exhibited growth inhibition against several bacteria, fungi, and yeast species [144]. The highest inhibition zone diameter was verified against S. enterica, and ommatins, specifically of the xanthommatin type, were suggested as the main active compounds [144].

4. Cytotoxicity of Natural Antimicrobial Lipids against Mammalian Cells

Some lipid and lipid-rich extracts from natural sources showed high MIC and MBC values, in the range of mg/mL, as can be seen in Table 2, Table 4, and Table 6. This is more than one thousand times larger than is of pharmaceutical significance and raises an important question regarding cytotoxicity to mammalian cells and safety to human beings. Some studies emphasized the low toxicity to eukaryotic cells of antimicrobial lipids from natural sources, namely of FA [158]. But most studies that searched for natural lipids with antimicrobial activity did not perform in vitro or in vivo cytotoxicity experiments. Data regarding mammalian cytotoxicity are not yet available for most of these compounds, which is a limitation of the studies presented in this review about antimicrobial plant lipids. Most studies that tested antimicrobial and cytotoxicity activities from marine lipids are limited to lipid-rich extracts [145,194] or lipid-rich fractions [97,195]. For instance, petroleum ether fractions of Grateloupia livida extracts demonstrated a higher antibacterial activity and this fraction did not display acute oral toxicity in mice (100% survival rate at doses up to 2.0 g/Kg) [195]. Even so, careful conclusions should be taken from these evidences, since petroleum ether is a carcinogenic solvent. The MeOH and acetone fractions from O. obtusiloba demonstrated activity against HSV-1 and low toxicity to Vero cell (African Green monkey kidney cells) cultures, showing 50% cytotoxic concentration (CC50) of 172 and >200 µg/mL in MeOH and acetone fractions, respectively [97]. A sulfolipid-rich fraction from the same red macroalga showed a higher cytotoxicity with CC50 of 72 µg/mL in Vero cell lines [111]. SQDG fractions from S. vulgare with antiviral activity (HSV-1 and HSV-2), displayed CC50 > 200 µg/mL in Vero cells [119]. The ethanolic extract as well as the glycolipid, FA and pigments’ fractions from L. cichorioides demonstrated hemolytic activity at 200 µg/mL in erythrocytes of mongrel white mice [91]. SQDG(16:0/16:0) isolated from C. racemosa with antiviral activity (HSV-2) had very low toxicity to Vero cells ATCC CCL-81 with a CC50 of 1.0 g/mL [95]. An acetylenic FA isolated from the calcareous sponge P. cf. waguensis demonstrated weak cytotoxic effect against NBT-T2 rat bladder epithelial cells (IC50 > 20 mg/mL) [163]. FA mixtures isolated from the sponge A. oroides exhibited in vitro antiplasmodial, trypanocidal, and leishmanicidal activities with weak cytotoxicity toward mammalian (rat skeletal myoblast L6) cells (IC50 from 43 to >90 µg/mL) [162]. Sterols isolated from the sponge H. simulans demonstrated anti-mycobacterial and anti-trypanosomal activities, but low cytotoxicity on normal fibroblasts derived from human foreskin (Hs27) cells with IC50 ranges from 58 to >100 µM [170]. Meroterpene sulfate molecules isolated from the sponge Fasciospongia sp. was inactive (IC50 > 30 µM) toward human foreskin fibroblast (HFF-1) cell lines [186]. Finally, lipid extracts from different body compartments (hemolymph, hemocyte, eggs, muscle, and exoskeleton) of four marine crustaceans demonstrated hemolytic activity against human red blood cells, hemolymph and exoskeleton extracts being those that presented the highest activity [149].
Molecules, in this case lipids, with such high MIC values have little chance of undergoing clinical development. Nevertheless, the results of the reviewed reports should allow to focus on the most interesting molecules, having a low MIC value, and reserve the molecules with a high MIC value for other applications, such as veterinary clinic or agriculture.

5. Lipidomics for the Analysis of Bioactive Lipids in Plants and in Marine Organisms

The identification and characterization of lipids as natural antimicrobial agents is of utmost importance, either for their exploitation from natural sources or to understand their mechanisms of action. Lipid identification from natural sources is achieved by using lipidomic strategies. Lipidomics consists in the analysis, identification, and structural characterization of the lipid molecular species from a biological matrix, based on chromatography and MS techniques. It also involves optimizing extraction and fractionation processes, considering the polarity of the different lipids that make up the biological systems. As such, lipidomics is a valuable tool to discover bioactive lipids with antimicrobial activity.
The main phases of the lipidomics workflow include lipid extraction, fractionation, and/or enrichment steps, and analysis of total extracts or lipid fractions by MS combined with LC and/or GC (Figure 3).
Lipid extraction is usually performed with organic solvents. Mixtures of CHCl3, MeOH, and H2O are the most used, such as the Bligh and Dyer [196] or Folch [197] methods and their modifications. These methods are considered the most efficient to extract the total lipid content. However, there are other solvents used for lipid extraction, such as EtOH, MeOH, n-hexane, BuOH, EtOAc, giving rise to different lipid yields [198,199]. CHCl3 is being replaced by CH2Cl2 in these methods because the latter is less toxic and allows a similar extraction efficiency. The solvent or the mixture of solvents used in the extraction step(s) exert a great influence in the lipid composition of the extracts obtained from natural sources. In most cases, extractions with different solvents lead to crude extracts with the same components but in different amounts. It is also possible to selectively extract some lipid classes, such as the extraction performed with apolar solvents, as n-hexane, which recover mostly apolar lipids (e.g., triacylglycerols). Nevertheless, an effective extraction is very important for the identification of bioactive lipids. Non-conventional methods of extraction as ultrasound- and microwave-assisted extraction or SFE [63] are used to help the extraction, particularly to improve the lipids yield, or to obtain extracts with specific functions and applications. Assisted extraction methods are frequently combined with green solvents, such as EtOH. Soxhlet-assisted extraction with less polar solvents, such as n-hexane, is normally used to isolate lipophilic and more apolar lipids, as terpenoids and sterols. Testing potential antimicrobial lipid extracts obtained with different solvents, even from the same source, would provide dissimilar bioactive properties due to different lipid compositions.
Total lipid extracts include a great diversity of lipid classes and molecular species. Fractionation of the total lipid extracts to obtain fractions enriched with specific lipid classes can be achieved by solid-phase extraction (SPE), using columns of simple silica (SPE-SiO2) or functionalized silica, by preparative HPLC, or by TLC, although the latter is less common nowadays. TLC can also be used as an identification tool in lipid extracts or fractions, by applying spots of well-known lipid standards in the TLC plate and compare their retention factor with the samples’ bands after elution. However, it has the disadvantages of lacking information at lipid molecular level and being time-consuming [200]. A careful choice of the eluents and gradients allows obtaining a selective separation of lipid fractions from the initial extract. The fractions obtained can be used for diverse purposes: to quantify the different lipid classes (e.g., by gravimetry), to separate neutral lipids (e.g., triacylglycerols and sterols) from polar lipids (e.g., phospholipids, glycolipids), or to identify different phospholipid classes, that can be further separated by TLC and estimated by phosphorus quantification of each TLC spot. The lipid fractions can be then used to evaluate the bioactive properties of a specific lipid class and analyzed by GC-MS and/or LC-MS to provide an insight on the structure–activity relationship.
The characterization of total lipids or lipid fractions is done, nowadays, by MS-based approaches using several kinds of mass spectrometers coupled with chromatography. GC-MS is used to identify and quantify FA after derivatization (usually methylation) of apolar lipids as terpenoids and sterols (after derivatization by silylation). GC-MS allows the identification of these molecules by specific retention times, mass spectra analysis, and data base comparison. Nevertheless, GC-MS neither covers large molecules nor non-volatile molecules. Thus, when this approach is used to characterize bioactive lipids, a lot of information is missing. LC-MS allows a broader coverage than GC-MS of lipid species and larger molecules, usually the most abundant ones in the lipid extracts, such as triacylglycerols, polar lipids, or esterified sterols. Besides, small molecules like free FA and free sterols are also detected.
LC-MS identifies the lipid molecular species by their retention time, accurate molecular weight observed in the mass spectra (i.e., LC-MS level), and detailed structural features by interpretation of their LC-MS/MS spectra. The chromatographic peaks are integrated to plot the quantification of each molecular species, which is normalized by an appropriate internal standard to reach a relative quantification. Routine lipidomics analyses use reversed-phase (e.g., C18 or C30), normal-phase, or hydrophilic interaction liquid chromatography (HILIC) columns [200]. In the former, the elution of the lipid molecules is based on their FA composition. So, an overlap of molecular species from different lipid classes but presenting the same FA composition can occur. In the latter two types of columns, the lipid molecules are separated by their hydrophilic properties, allowing to separate the different lipid classes present in the sample, which will depend on the polar head features.
Recent developments in MS technologies permit to acquire a huge amount of data in a short time frame, covering more than three hundred lipid species in one single LC-MS run. This can be done by means of the high-resolution mass spectrometers Orbitrap or quadrupole-time-of-flight (Q-TOF), available for untargeted or targeted analysis, or the triple quadrupoles (QQQ) and Q-traps, that are more suitable for targeted analysis, i.e., quantification of previously selected molecular species. However, data analysis is still time-consuming because of the lack of universal and exhaustive lipidomics databases and software. Some databases and software currently used are the LIPID MAPS database, the MZmine, LipidBlast, LipoStar, LipidSearch, and LPPtiger software.
The identification of bioactive molecules from natural sources is a laborious work that requires performing extraction, bioassays, fractionation, and in some cases, identification, in a sequential way. This is to achieve a specific class of bioactive metabolites or, preferentially, a unique and well-defined bioactive molecule. This process is called bioassay-guided fractionation and is emerging in the field of drug discovery from natural sources [201]. This approach usually starts with different extracts obtained by using solvents with different polarities, in order to have a set of extracts enriched in different types of metabolites. These extracts are evaluated for their putative bioactivities and the one(s) with the highest activity is(are) further fractionated and the new fractions are assayed. The bioassay-fractionation-bioassay sequence can go around until a promising candidate molecule or family of molecules are considered and then it is characterized. The first step of fractionation is typically a liquid–liquid extraction (solvent–solvent partition), and normally uses chromatography techniques, as TLC and column chromatography [201,202,203]. Isolated fractions are assayed afterwards. A final deep characterization using MS and NMR spectroscopy will reveal the exact structure of the bioactive molecule(s). This workflow will be a valuable tool to guide new drug discoveries and for understanding the structure-activity relationships. In this regard, lipidomics represents a valuable platform to advance in the characterization of lipid structures, survey lipid pathways, and can help in the elucidation of the interaction of lipids with microorganisms’ membranes, because of the high sensitivity and selectivity of MS.

6. Prospection and Applications of Antimicrobial Lipids

Several antimicrobial lipids are commercially available or can be used in different formulations in the cosmetic, pharmaceutical, and food industries, as well as in agriculture and aquaculture.

6.1. Cosmetic and Drug Formulations

In cosmetics, the free FA 10:0 and 12:0 and their corresponding MAG, monocaprin MAG(10:0) and monolaurin MAG(12:0), respectively, are commonly used in topical applications [21]. As a general rule, the esterification of free FA to glycerol increases the antimicrobial activity [127]. MAG(10:0) has been suggested as an ingredient for drug formulations to avoid oral infections by C. albicans [204].

6.2. Food Additives

The free FA 8:0 (commercial lipid standard) was shown to be effective against E. coli, Salmonella and other foodborne pathogens [21]. MAG(10:0) is known as a safe food additive, widely used as an emulsifier in the food industry [205].
Lipid extracts from marine organisms demonstrated to be a source of antibacterial compounds. The FA 16:1 inhibited the growth of the foodborne pathogens Bacillus cereus and B. weihenstephanensis [125]. Extracts from the microalga D. salina inhibited the growth of important food industry pathogens (i.e., E. coli, S. aureus, C. albicans, and A. niger) [123]. EPA, a high abundant PUFA in marine species, presented a potent action against the foodborne pathogen B. cereus, likely by disrupting the pathogen’s cell membrane, ultimately leading to cell lysis [206].

6.3. Herbicides and Pesticides

Some studies evaluated the antimicrobial activity of plants’ lipid extracts against both phytopathogenic fungi and bacteria. The sphingolipid [(2S,3S,4R,10E)-2-[(2’R)-2-hydroxytetracosanoylamino]-1,3,4-octadecanetriol-10-ene], a low polarity aglycone isolated from cucumber (C. sativus) stems, had strong antibacterial and antifungal activity against plant pathogens [74]. A mixture of lipids (FA, FAME, squalene, and β-sitosterol) extracted from andiroba (Carapa sp.) seeds demonstrated a MIC range of 156–250 µg/mL against several phytopathogenic fungi: A. flavus, A. niger and F. oxysporum [58]. Antimicrobial compounds from plants are envisioned as eco-friendly alternatives to chemical pesticides that harm both the environment and public health [58], because of their structural diversity, unique bioactivity, and environmental compatibility [74]. It is, thus, necessary to invest in a new approach to understand the mode of action of antimicrobial lipids isolated from plants in microbial cells.
Marine macroalgae have been traditionally used by several populations as soil fertilizers in agriculture, enriching them with minerals and plant growth promoters. The presence of antimicrobial molecules in macroalgae may contribute to develop biologically active compounds that protect agricultural crops toward pathogenic bacteria and fungi. This is the case of the sulfolipids isolated from the brown macroalga S. wightii that showed activity against the Gram-negative bacterium Xanthomonas oryzae pv. oryzae that causes the bacterial blight of rice [120]. Specific glycolipids, termed caminosides, isolated from the marine sponge C. sphaeroconia were active against the plant pathogen Pythium ultimum, the cause of damping off and root rot diseases in food crops and ornamental species [176]. Three sesterterpenes identified in the sponge Thorectandra sp. showed high inhibitory effect against the plant pathogenic fungus Cladosporium herbarum [190].
A recent study has mapped soil-borne fungal plant pathogens and projected their distribution under different climate change and soil uses scenarios [207]. The most dominant pathogens that harm global crop production belong to the genera Alternaria and Fusarium [207]. Enriched fractions of glycolipids from the macroalgae L. cichorioides and S. pallidum, as well as free FA and PUFA fractions from L. cichorioides, and FA esters, triacylgycerols/free sterols, free sterols and diacylglycerol fractions from S. pallidum demonstrated activity against the fungus F. oxysporum [91,118]. Lipid fractions with several steroid compounds from the oyster S. glomerata were very active against Fusarium sp. [171]. A bioprospection study in macroalgae of the order Caulerpales isolated ten sesquiterpenoids and diterpenoids and tested their activity in several bacterium and fungi strains. Eight of these compounds inhibited the growth of Alternaria sp. [98].
The free FA 10:0, 12:0, and their corresponding MAG [MAG(10:0) and MAG(12:0)], likewise as for cosmetic applications as mentioned above, are also used in agriculture crops as herbicides [21].

6.4. Aquaculture

Nowadays, aquaculture production accounts for almost half of the animal and aquatic plants catches, with 82 million tons [208]. Aquaculture represents an important food production sector, so finding environmental-friendly compounds with antibiotic activity instead of synthetic drugs is of utmost importance. This is even more urgent if we consider that, although vaccination is the best alternative to prevent infectious diseases in general, in aquaculture it is not likely to protect juvenile fish (without a mature immune system), shrimp, and bivalves (without an adaptive immune system, only with innate system), which are the most affected aquaculture animals by infectious diseases.
Several antimicrobial compounds identified in marine organisms are salt-tolerant [14] and have demonstrated to be efficient against aquaculture-relevant pathogens such as Listonella anguillarum, Lactococcus garvieae, and Vibrio species, showing advantage in pathogen control of fish and shellfish farming [99,108,112,125,126,209]. Extracts of Falkenbergia, a heteromorphic sporophyte of Asparagopsis taxiformis, inhibited the growth of several fish and shrimp Vibrio pathogens [106]. The FA 16:3 n-4 (HTA) isolated from the diatom P. tricornutum inhibited the growth of the Gram-negative marine pathogenic bacterium L. anguillarum [125]. A lipid fraction of the oyster S. glomerata extract inhibited the shrimp white spot syndrome virus (WSSV) in Fenneropenaeus indicus [171].

7. Conclusions

Lipids isolated from plants and marine organisms have demonstrated a broad spectrum of antimicrobial activities. These biomolecules can be envisaged as a promising alternative to help control pathogenic microbial infections. They have shown positive results in in vitro studies and microorganisms do not develop resistance to them, as far as it is known. However, the study of natural sources-derived antimicrobial lipids presents yet some shortcomings. There is a low number of systematic studies performing the isolation of pure lipid molecular species and their structural characterization, since they are mainly studied as complex extracts. There is also a lack of in vivo tests, indispensable to understand their mechanism of action, their cytotoxicity to eukaryotic cells, and consequently allowing their use at a large scale. Lipidomics is a fundamental tool to advance in the characterization of lipid structures and elucidate the lipids–microorganisms’ interaction. This can be achieved along with complementary biophysical, spectroscopic, and spectrometric studies that will be useful to understand their mechanism of action toward microbes and to define the structure–activity relationship. In addition, it is necessary to study the synergistic effects of these compounds against a wide range of microorganisms’ species to evidence broad-spectrum effects. The bioprospection of new natural lipids will benefit from the association among complementary research areas and the industry. Furthermore, the potential applications of antimicrobial lipids in different economic sectors, such as pharmaceutical, cosmetics, agriculture, or aquaculture, are still underexplored. So, the combination of these natural resources with sophisticated analytical tools applied to lipidomics research will open new perspectives on antimicrobial lipids for clinical and non-clinical applications. It is hoped that the future could bring about a greater interaction between lipidomics and natural chemotherapy to reveal the true microbicidal action of lipids toward pathogens. More studies must be done to understand which lipids can effectively be responsible by the inhibitory or microbicidal effect and their structure–activity relationship.

Author Contributions

Conceptualization and study design, E.A., F.R., and M.d.R.D.; literature search and review, E.A., F.R., M.D., and D.L.; writing—original draft preparation, E.A., F.R., and M.d.R.D.; writing—review and editing, E.A., F.R., M.d.R.D., A.A.; formatting and design—D.L.; supervision, A.A. and M.d.R.D. All authors read and approved the final version of the manuscript.

Funding

The authors acknowledge the University of Aveiro, Fundação para a Ciência e a Tecnologia (FCT, Portugal) and Ministério da Ciência e Tecnologia (MCT) for the financial support for the Química Orgânica, Produtos Naturais e Agroalimentares (QOPNA) research Unit (FCT UID/QUI/00062/2019), LAQV-REQUIMTE (FCT UIDB/50006/2020) and CESAM [UIDB/50017/2020.UIDP/50017/2020] through national founds and, where applicable, co-financed by the European Regional Development Fund (FEDER), within the Portugal 2020 Partnership Agreement, and to the Portuguese Mass Spectrometry Network (RNEM, LISBOA-01-0145-FEDER-402-022125). Thanks are also due to FCT/MCT through national funds (PIDDAC), and the co-funding by FEDER, within the Portugal 2020 Partnership Agreement and Programa Operacional Temático Factores de Competitividade (COMPETE) 2020. Diana Lopes (reference SFRH/BD/119027/2016) is grateful to FCT, Programa Operacional do Capital Humano (POCH) and European Union through European Social Fund (FSE) for her PhD grant. This work was also funded by national funds, through FCT, in the scope of the Individual Call to Scientific Employment Stimulus 2017 with a Junior Researcher contract to Eliana Alves (reference CEECIND/00971/2017) and to Felisa Rey (reference CEECIND/00580/2017).

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

AMPAntimicrobial peptide
AMRAntimicrobial resistance
BuOHButanol
CCCytotoxic concentration
CH2Cl2Dichloromethane
CHCl3 Chloroform
CLSIClinical and Laboratory Standards Institute (formerly NCCLS)
COSYCorrelation spectroscopy
CRECarbapenemase-resistant Enterobacteriaceae
DAGDiacylglycerol
DGDGDigalactosyldiacylglycerol
DOXDioxygenase
DPADocosapentaenoic
ECEffective concentration
EPAEicosapentaenoic acid
ESBLExtended-spectrum beta-lactamase
ESI-MSElectrospray ionization-mass spectrometry
ESI-MS/MSElectrospray ionization-tandem mass spectrometry
ETAEicosatetraenoic acid
Et2ODiethyl ether
EtOAcEthyl acetate
EtOHEthanol
FAFatty acid
FAB-MSFast atom bombardment-mass spectrometry
FAMEFatty acid methyl ester
FIA-MSFlow-injection analysis-mass spectrometry
FT-NMRFourier transformed-nuclear magnetic resonance
G(-)Gram-negative
G(+)Gram-positive
GCGas-phase chromatography
GC-FIDGas-phase chromatography-flame ionization detector
GC-MSGas-phase chromatography-mass spectrometry
GlCerGlucosylceramide
GRASGenerally recognized as safe
HMBCHeteronuclear multiple bond correlation
HPLCHigh-performance liquid chromatography
HPLC-DADHigh-performance liquid chromatography-diode-array detector
HPLC-ELSDHigh-performance liquid chromatography-evaporative light scattering detector
HPLC-ESI-MSHigh-performance liquid chromatography-electrospray ionization-mass spectrometry
HPLC-UV-HRMSHigh-performance liquid chromatography-ultraviolet-high-resolution mass spectrometry
HPTLCHigh-performance thin-layer chromatography
HR-APCI-MSHigh-resolution atmospheric pressure chemical ionization-mass spectrometry
HR-EI-MSHigh-resolution-electron ionization-mass spectrometry
HR-FAB-MSHigh-resolution fast atom bombardment-mass spectrometry
HRMSHigh resolution mass spectrometry
HSQCHeteronuclear single quantum coherence
HSVHerpes simplex virus
HSV-1Herpes simplex virus type 1
HSV-2Herpes simplex virus type 2
IC50Half maximal inhibitory concentration
IMTAIntegrated multi-trophic aquaculture
IRInfrared
IZInhibition zone
LCLiquid chromatography
LC-MS/MSLiquid chromatography-tandem mass spectrometry
LC50Lethal concentration (ppm) at 50%
LOXLipoxygenase
LPCLysophosphatidylcholine
MAGMonoacylglycerol
MBCMinimum bactericidal concentration
MDRMulti-drug resistant
MeOHMethanol
MFCMinimum fungicidal concentration
MGDGMonogalactosyldiacylglycerol
MIC Minimum inhibitory concentration
MIQ Minimum inhibition quantity
MRSAMethicillin-resistant Staphylococcus aureus
MSSAMethicillin-sensitive Staphylococcus aureus
MUFAMonounsaturated fatty acid
NCCLSNational Committee for Clinical Laboratory Standards
NMRNuclear magnetic resonance
NOESYNuclear Overhauser effect spectroscopy
PACTPhotodynamic antimicrobial chemotherapy
PAF Platelet-activating factor
PC-OPhosphatidylcholine ether
PEPhosphatidylethanolamine
PFA Paraformaldehyde
PI Phosphatidylinositol
ppmParts per million
PrOHPropanol
PSPhosphatidylserine
PUFAPolyunsaturated fatty acid
QSI Quorum sensing inhibitor
RPReversed-phase
SEC Size exclusion chromatography
SFE Supercritical fluid extraction
SI Selectivity index
SiO2 Silica gel
SMSphingomyelin
SPE Solid-phase extraction
SQDG Sulfoquinovosyldiacylglycerol
TI Therapeutic index
TLC Thin-layer chromatography
UFAUnsaturated fatty acid
VIIViral inhibition index
WHOWorld Health Organization

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Figure 1. Infographic of the actual state-of-the-art on antibiotic resistance and search for novel antimicrobials, as natural product-derived lipids. Abbreviations: MDR, multidrug resistant; UN, United Nations; AMP, antimicrobial peptides; PACT, photodynamic antimicrobial chemotherapy; FA, fatty acids; MAG, monoacylglycerols; TP, terpenoids; SG, steroidal glycosides.
Figure 1. Infographic of the actual state-of-the-art on antibiotic resistance and search for novel antimicrobials, as natural product-derived lipids. Abbreviations: MDR, multidrug resistant; UN, United Nations; AMP, antimicrobial peptides; PACT, photodynamic antimicrobial chemotherapy; FA, fatty acids; MAG, monoacylglycerols; TP, terpenoids; SG, steroidal glycosides.
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Figure 2. Chemical structures of the different lipid classes isolated from natural sources with antimicrobial activity.
Figure 2. Chemical structures of the different lipid classes isolated from natural sources with antimicrobial activity.
Antibiotics 09 00441 g002aAntibiotics 09 00441 g002bAntibiotics 09 00441 g002c
Figure 3. Workflow summarizing the main techniques used for lipidomics analyses of lipids from plants and marine organisms.
Figure 3. Workflow summarizing the main techniques used for lipidomics analyses of lipids from plants and marine organisms.
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Table 1. Plant potential antimicrobial lipids or lipid-rich extracts, their origin and extraction method grouped by botanic family.
Table 1. Plant potential antimicrobial lipids or lipid-rich extracts, their origin and extraction method grouped by botanic family.
Botanical Name Family Common Name Country of Collection Plant PartExtracting Solvent/MethodIsolated Lipids or Lipid MixturesRef.
Sesuvium portulacastrum L.AizoaceaeSea purslaneIndiaLeavesMeOH/benzene/sulfuric acid (200:100:10, v/v)FAME[60]
Blutaparon portulacoides (A. St.-Hil.) MearsAmaranthaceaeCapotiraguáBrazilRootsEtOHAcyl steryl glycosides (sitosteryl 3-β-O-glucoside 6’-O-palmitate and stigmasteryl 3-β-O-glucoside 6’-O-palmitate)[70]
Arthrocnemum indicum (Willd.) Moq., Salicornia brachiata Roxb., Suaeda maritima (L.) Dumort. and Suaeda monoica Forsk.Glasswort for Salicornia genus, herbaceous seepweed for S. maritima, and South-Indian seepweed for S. monoicaIndiaShoots of A. indicum and S. brachiata, and leaves of S. maritima and S. monoicaDry MeOH/benzene/sulfuric acid (200:100:10, v/v)FAME[61]
Alternanthera brasilianaBrazilian joyweedBrazilRoot, stem and leavesEtOH and EtOAcLinoleate oxylipins[65]
Phoenix dactylifera L.ArecaceaeDate palmIndiaSeedsCHCl3 and acetoneSterol and triterpenes[66]
Asphodelus aestivus Brot.Asphodelaceae (formerly Liliaceae)Summer asphodelTurkeySeedsPetroleum ether with Soxhlet extractorFA (C4:0, 6:0, 8:0, 10:0, 16:0, 18:0, 21:0, 24:0, 14:1, 15:1, 18:1n9t, 20:1, 24:1, 18:2, 18:2n6t, 18:2n6c, 20:2n6, 20:3n3, 22:6n3, and others unidentified)[54]
Artemisia incisa Pamp.Asteraceae PakistanRootsMeOH and recovered after elution on a SiO2 column with CH2Cl2/MeOH (9:1, v/v) following previous elution with n-hexane/EtOAc (5:4, v/v)Artemceramide-B[73]
Pteranthus dichotomus Forssk. (also known as P. echinatus Desf.)Caryophyllaceae Algerian SaharaAerial partsMeOH/H2O (80:20, v/v). Aqueous phase extracted successively with petroleum ether, EtOAc and n-BuOH. EtOAc fraction contained the sterols and steryl glycoside. BuOH fraction contained the glyceroglycolipids and the cerebroside.BuOH fraction contained the compounds: 1-O-palmitoyl-3-O-(6-sulfo-α-D-quinovopyranosyl)-glycerol, 1,2-di-O-palmitoyl-3-O-(6-sulfo-α-D-quinovopyranosyl)-glycerol and soya cerebroside I. EtOAc fraction contained the compounds: stigmat-7-en-3-ol, spinasterol, β-sitosterol and β-sitosterol-3-O-glycoside[78]
Cucumis sativus L.CucurbitaceaeCucumberChinaStemsCHCl3 fraction of the crude methanolic extractSphingolipids [(2S,3S,4R,10E)-2-[(2’R)-2-hydroxytetracosanoylamino]-1,3,4-octadecanetriol-10-ene, 1-O-β-D-glucopyranosyl-(2S,3S,4R,10E)-2-[(2’R)-2-hydroxytetracosanoylamino]-1,3,4-octadecanetriol-10-ene and soya-cerebroside I][74]
Excoecaria agallochaEuphorbiaceaeBlind-your-eye mangroveIndiaLeavesDry MeOH, benzene and sulfuric acid (200:100:10, v/v)FAME[62]
Albizia adianthifolia (Schumach) and Pterocarpus angolensis (DC)FabaceaeFlat crown Albizia and African teak, respectivelyNigeria and Botswana, respectivelyHeartwood of A. adianthifolia and stem bark of P. angolensisn-hexane, CHCl3, MeOH, and 10% MeOH (aq)n-hexadecanoic acid (palmitic acid); oleic acid; chondrillasterol; stigmasterol, 24S 5α-stigmast-7-en-3-ol; 9,12-octadecadienoic acid (Z,Z)-, methyl ester; trans-13-octadecanoic acid, methyl ester; tetradecanoic acid; hexadecanoic acid, methyl ester; octadecanoic acid[79]
Baphia massaiensisJasmine peaBotswanaSeedsn-hexane/1-propanol (3:1, v/v) with Soxhlet extractorSeed oil (total FA)[80]
Cassia tora L. (or Senna tora L. Roxb.)Sickle SennaIndiaLeaves and stemPetroleum ether with Soxhlet extractorFA (the major were palmitic acid, linoleic acid, linolenic acid, margaric acid, melissic acid, and behenic acid)[55]
Trigonella foenum-graecum L.FenugreekIndiaSeedsSupercritical fluid extraction (40–60 °C and 10–25 Mpa)Conjugated linoleic acid methyl ester, saturated FAME, steroids[63]
Quercus leucotrichophora A. CamusFagaceaeBanjh oakIndiaFruits85% aqueous EtOH. Ethanolic extract fractionated with hexane and EtOAc using Soxhlet extractor. Hexane extract was analyzed.FAME[56]
Quercus leucotrichophora A. CamusBanjh oakGarhwal region of HimalayaLeaves and barkMeOHFA; linoleic acid in stem bark and leaves extracts and cis-vaccenic acid in stem bark[81]
Vitex altissima L., V. negundo L. and V. trifolia L.LamiaceaePeacock chaste tree, Chinese chaste tree, and simpleleaf chastetree, respectivelyIndiaLeavesDry MeOH/benzene/sulfuric acid (200:100:10, v/v)FAME[64]
Linum usitatissimum L. LinaceaeCommon flax or linseedAlgeriaSeedsPetroleum ether with Soxhlet extractorFAME[57]
Scaphium macropodum (Miq.) Beumee ex. HeyneMalvaceaeMalva nut or Kembang semangkokMalaysiaStem barkMeOHMethyl hexadecanoate, hexadecanoic acid <n->[82]
Melastoma malabathricum L.MelastomataceaePlanter’s rhododendron or SendudokMalaysiaLeavesMeOH/H2O (4:1, v/v), defatted with petroleum ether and extracted with CHCl3. Lipids recovered after elution of the CHCl3 extract by SiO2 column with CHCl3/acetone/MeOH (10:9:1, v/v).Steryl glycoside:
β-sitosterol 3-O-β-D-glucopyranoside
[69]
Azadirachta indica A. JussMeliaceaeNeemIndiaLeavesMeOH. Recovered after elution on a SiO2 column with CHCl3/MeOH (9:1, v/v)SQDG[71]
Azadirachta indica A. JussNeemIndiaLeavesPetroleum ether (60–80 °C) for 24 h and extracted thrice with MeOH for 48 h each time at room temperatureSQDG[72]
Carapa guianensis Aubl. and Carapa vasquezii KenfackAndiroba BrazilSeed oiln-hexane with Soxhlet extractorFA, FAME, squalene, β-sitosterol[58]
Ficus lutea Vahl MoraceaeGiant-leaved fig or Lagos rubbertreeCameroonWoodsCH2Cl2/MeOH (1:1, v/v) and elution with EtOAc/10% MeOHGlycosphingolipid [1-O-β-D-glucopyranosyl-(2S,3R,5E,12E)-2N-[(2′R)-hydroxyhexadecanoyl]-octadecasphinga-5,12-dienine] named lutaoside[76]
Ficus pandurata HanceFiddle leaf figEgyptFruits70% MeOH. MeOH extract fractionated on a SiO2 column and purified by semi-preparative HPLC to afford pure ceramidesCeramides [panduramides A-D, and newbouldiamide][75]
Kunzea ericoides (A. Rich) J. ThompsonMyrtaceaeKanuka
(Maori), white manuka (Maori) or the white tea tree
(English)
AustraliaLeaves and twigsCH2Cl2:MeOH (1:1, v/v), CH2Cl2:MeOH (2:1, v/v) and CH2Cl2 (neat)Steryl esters, triacylglycerols, free FA, sterols, and phospholipids[77]
Pentagonia gigantifolia DuckeRubiaceae PeruRoots95% EtOH. EtOH extract was fractionated on a SiO2 column using CHCl3/MeOH from 0% to 100% MeOH. Fraction eluted with 2% MeOH/CHCl3 was separated on C18 SiO2 using 85% to 90% MeOH.Acetylenic acids: 6-octadecynoic acid and 6-nonadecynoic acid[38]
Hedyotis pilulifera (Pit.) T.N. Ninh VietnamAerial partsMeOH at 60 °C, suspended in water and successively partitioned with CHCl3 and EtOAc. EtOAc extract fractionated on a SiO2 column.Triterpenoids, steroids, FA, glycolipids, and a ceramide[83]
Withania somnifera (L.) Dunal, Euphorbia hirta L., Terminalia chebula Retz.Solanaceae, Euphorbiaceae, CombretaceaeAshwaganda, asthma-plant, black myrobalanIndiaFruits, leaf, stem, and root from W. somnifera and E. hirta and fruits, leaf, stem, and stem bark from T. chebulaEtOAcSterols fraction[67]
Kaempferia pandurata Roxb. (synonym of Boesenbergia rotunda (L.) Mansf.) and Senna alata (L.) Roxb.Zingiberaceae and Fabaceae, respectivelyFingerroot and candle bush, respectivelyIndonesiaLeaf of S. alata and rhizome of K. pandurataEtOH (96%)Sterols and triterpenoid[68]
Zygophyllum oxianum Boriss.ZygophyllaceaeBeancaperUzbekistanLeaves, stems, and fruitAcetone and CHCl3:MeOH (2:1, v/v) for total lipid extraction. Total lipids from each plant part separated in SiO2 columns. Neutral lipids eluted with CHCl3; glycolipids with acetone; phospholipids with MeOH.Total lipid extract from leaves, stems and aerial organs (hydrocarbons, triterpenol and steryl esters, triacylglycerols, free FA, sterols, phospholipids)[59]
Table 2. Antimicrobial activity of plant lipids or plant lipid-rich extracts.
Table 2. Antimicrobial activity of plant lipids or plant lipid-rich extracts.
Botanical Name Tested (Micro)OrganismsAntimicrobial Testing Method/EvaluationReference Antimicrobial (Positive Control)MIC, MBC, Diameter of Inhibition Zone (in mm) or OtherIsolated Lipids or Lipid MixturesRef.
Sesuvium portulacastrum L.G(+) bacteria: Bacillus subtilis NCIM 2063, B. pumilus NCIM 2327, Micrococcus luteus NCIM 2376 and S. aureus NCIM 2901; G(-) bacteria: P. aeruginosa NCIM 5031, K. pneumoniae NCIM 2957 and E. coli NCIM 2256. Ten isolates of MRSA and of MRSA NCTC 6571. Human pathogenic yeast type fungi: Candida albicans, C. krusei, C. tropicalis and C. parapsilosis and mould fungi: Aspergillus niger, A. flavus, and A. fumigatusInhibition zone (IZ) by disk diffusion test and minimum inhibitory concentration (MIC) by broth macrodilution methodCiprofloxacin for bacteria, methicillin, oxacillin and vancomycin for MRSA and amphotericin-B for fungiMIC: 0.25 mg/mL for B. subtilis, 0.5 mg/mL for S. aureus, MRSA, P. aeruginosa, K. pneumoniae and C. albicans, and 1.0 mg/mL for E. coli; MBC: 0.5 mg/mL for B. subtilis, 1.0 mg/mL for S. aureus, MRSA and K. pneumoniae, and 2.0 mg/mL for P. aeruginosa and E. coli; MFC: 1 mg/mL for C. albicansFAME[60]
Blutaparon portulacoides (A. St.-Hil.) MearsTrypanosoma cruzi, Leishmania amazonensis, S. aureus ATCC 25923 and 7+ penicillinase producer, Streptococcus epidermidis (6ep), E. coli ATCC 10538, Streptococcus mutans (9.1), Streptococcus sobrinus (180.3)Crude extracts and isolated compounds added to the trypomastigote-containing blood samples and incubated 24 h at 4 °C. Trypanocidal activity evaluated by counting the remaining trypomastigotes. L. amazonensis amastigote viability assessed colorimetrically by the reduction of a tetrazolium salt (MTT). Antimicrobial activity measured by the well-diffusionmethod in double layerGentian violet for trypanocidal activity and gentamicin for antibacterial assaysMIC: 100–500 μg/mL in T. cruzi trypomastigotes and 14–500 μg/mL in L. amazonensis amastigotes; 50 μg/mL in E. coli, S. aureus ATCC 25923, S. aureus (7+) and 500 μg/mL in S. epidermidis, S. mutans, and S. sobrinusAcyl steryl glycosides (sitosteryl 3-β-O-glucoside 6’-O-palmitate and stigmasteryl 3-β-O-glucoside 6’-O-palmitate)[70]
Arthrocnemum indicum (Willd.) Moq., Salicornia brachiata Roxb., Suaeda maritima (L.) Dumort. and Suaeda monoica Forsk.G(+) bacteria: B. subtilis NCIM 2063, B. pumilus NCIM 2327, M. luteus NCIM 2376, and S. aureus NCIM 2901; G(-) bacteria: P. aeruginosa NCIM 5031, K. pneumoniae NCIM 2957, and E. coli NCIM 2256; ten isolates of MRSA and of MRSA NCTC 6571; yeasts (C. albicans, C. krusei, C. tropicalis, and C. parapsilosis) and molds (A. niger, A. flavus, and A. fumigatus)Disk diffusion method and broth macrodilution methodCiprofloxacin for bacteria, methicillin, oxacillin and vancomycin for MRSA and amphotericin-B for fungiMIC of 0.06 mg/mL of S. brachiata extracts against B. subtilis, S. aureus, and MRSA, and 0.5 mg/mL against P. aeruginosa; MIC of 0.5 mg/mL of all FAME extracts against E. coli and K. pneumoniae; MBC of 0.1 mg/mL of S. brachiata extracts against P. aeruginosa and of 1.0 mg/mL of all FAME extracts against E. coli and K. pneumoniaeFAME[61]
Alternanthera brasilianaE. coli ATCC 25922, B. subtilis ATCC 6623, P. aeruginosa ATCC 15442, M. luteus ATCC 9341, and S. aureus ATCC 25923Microdilution broth method according to NCCLS standardizationTetracycline and norfloxacinMIC: 50 μg/mL against B. subtilis, M. luteus, and S. aureusLinoleate oxylipins[65]
Phoenix dactylifera L.Bacillus cereus and E. coliDisk diffusion methodStreptomycin20 mm against E. coli and 17 mm against B. cereus at 1 mg/mL of the acetone extractSterol and triterpenes[66]
Asphodelus aestivus Brot.G(+) bacteria: S. aureus ATCC 6538-p, E. faecalis ATCC 29212; G(-) bacteria: E. coli ATCC 29998, K. pneumoniae ATCC 13883, P. aeruginosa ATCC 27853); yeasts: C. albicans ATCC 10239 and C. krusei ATCC 6258Disk diffusion method and broth microdilution tests according to the recommendations of Clinical and Laboratory Standards Institute (CLSI)Ampicillin, ciprofloxacin and fluconazoleMIC: 512 μg/mL against S. aureus, E. faecalis, K. pneumoniae, and C. albicansFA (4:0, 6:0, 8:0, 10:0, 16:0, 18:0, 21:0, 24:0, 14:1, 15:1, 18:1n9t, 20:1, 24:1, 18:2, 18:2n6t, 18:2n6c, 20:2n6, 20:3n3, 22:6n3, and others unidentified)[54]
Artemisia incisa Pamp.S. epidermidis and S. aureusAgar well diffusion method and MIC determined by a referenced methodStreptomycin and tetracyclineS. epidermidis (0.0157 mg/mL) and S. aureus (0.0313 mg/mL)Artemceramide-B[73]
Pteranthus dichotomus Forssk. (also known as P. echinatus Desf.)S. aureus ATCC 25923, E. coli ATCC 25922, K. pneumoniae ESBL, and Enterobacter sp. ESBLDisk diffusion methodGentamicin and ampicillinP. dichotomus BuOH extracts at 0.25 g/mL (8 mm against E. coli, K. pneumoniae ESBL); P. dichotomus EtOAc extract at 0.5 g/mL (7 mm against E. coli), at 65 mg/mL (8.33 mm against S. aureus), and at 0.25 g/mL (7 mm against Enterobacter sp. ESBL)BuOH fraction contained 1-O-palmitoyl-3-O-(6-sulfo-α-D-quinovopyranosyl)-glycerol, 1,2-di-O-palmitoyl-3-O-(6-sulfo-α-D-quinovopyranosyl)-glycerol and soya cerebroside I. EtOAc fraction contained stigmat-7-en-3-ol, spinasterol, β-sitosterol and β-sitosterol-3-O-glucoside[78]
Cucumis sativus L.Phytopathogenic fungi (Pythium aphanidermatum, Botryosphaeria dothidea, Fusarium oxysporum f.sp. cucumerinum, and Botrytis cinerea); phytopathogenic bacteria [G(-): Xanthomonas vesicatoria ATCC 11633, Pseudomonas lachrymans ATCC 11921, and G(+) B. subtilis ATCC 11562]Mycelial radial growth inhibition assay and antifungal activity (pour plating method in potato dextrose agar medium) for fungi and agar-well diffusion assay for bacteriaCarbendazim for fungi and streptomycin sulfate for bacteria5.5–100 inhibitory rate of mycelia growth inhibitory activity; IC50 of B. subtilis (50.2–110.9 μg/mL), X. vesicatoria (25.6–64.5 μg/mL), P. lachrymans (15.3–37.3 μg/mL) for sphingolipidsSphingolipids [(2S,3S,4R,10E)-2-[(2’R)-2-hydroxytetracosanoylamino]-1,3,4-octadecanetriol-10-ene, 1-O-β-D-glucopyranosyl-(2S,3S,4R,10E)-2-[(2’R)-2-hydroxytetracosanoylamino]-1,3,4-octadecanetriol-10-ene and soya-cerebroside I][74]
Excoecaria agallochaG(+) bacteria: B. subtilis NCIM 2063, B. pumilus NCIM 2327, M. luteus NCIM 2376, S. aureus NCIM 2901; G(-) bacteria: P. aeruginosa NCIM 5031, K. pneumoniae NICM 2957, and E. coli NCIM 2256; yeasts: C. albicans, C. krusei, C. tropicalis, and C. parapsilosisDisk diffusion method for antibacterial and antifungal susceptibility tests; MIC tested in Mueller-Hinton broth for bacteria and yeast nitrogen base for yeasts by two-fold serial dilution methodCiprofloxacin and amphotericin BMIC: 0.125 mg for B. subtilis and S. aureus, 0.5 mg for P. aeruginosa and K. pneumoniae, and 1.0 mg for E. coli; MBC: 0.25 mg for B. subtilis and S. aureus, 1.0 mg for P. aeruginosa and K. pneumoniae, and 2.0 mg for E. coli; MFC: 1 mg for C. albicans, C. krusei and C. parapsilosis FAME[62]
Albizia adianthifolia (Schumach) and Pterocarpus angolensis (DC)Bacteria (E. coli, P. aeruginosa, B. subtilis, S. aureus) and yeast (C. albicans)Modified agar overlay methodChloramphenicol for bacteria and miconazole for fungiMIQ: 1 μg of n-hexane and CHCl3 extracts of A. adianthifolia against E. coli; 50 μg of n-hexane and CHCl3 extracts of A. adianthifolia against P. aeruginosa; 50 μg of CHCl3 extract of P. angolensis against B. subtilis and 100 μg of n-hexane extract of P. angolensis against B. subtilis and C. albicansn-hexadecanoic acid (palmitic acid); oleic acid; chondrillasterol; stigmasterol, 24S 5α-stigmast-7-en-3-ol; 9,12-octadecadienoic acid (Z,Z)-, methyl ester; trans-13-octadecanoic acid, methyl ester; tetradecanoic acid; hexadecanoic acid, methyl ester; octadecanoic acid[79]
Baphia massaiensisE. coli, B. subtilis, P. aeruginosa, S. aureus, and C. albicansAgar well diffusion methodNot mentioned10 mm of inhibition zone against E. coli and S. aureus, and 16 mm against B. subtilisSeed oil (total FA)[80]
Cassia tora L. (or Senna tora L. Roxb.)MRSA, MSSA, B. subtilis, and P. aeruginosaBroth microdilution methodAmpicillinMIC for all bacteria between 125–1000 μg/mL FA (the major were palmitic acid, linoleic acid, linolenic acid, margaric acid, melissic acid, and behenic acid)[55]
Trigonella foenum-graecum L.G(-) bacteria: E. coli and P. aeruginosa; G(+) bacteria: S. aureus and Streptococcus pyogenes; acid-fast bacteria: M. tuberculosis; fungi: C. albicans, A. niger and A. clavatus; parasite Plasmodium falciparum (etiological agent of malaria)Antimicrobial activity assessed by broth dilution method, anti-tuberculosis activity assessed by the slope method, in vitro anti-malarial assay according to a microassay protocolGentamycin, chloramphenicol, ciprofloxacin and norfloxacin for bacteria; isoniazid and rifampicin for mycobacteria; nystatin and greseofulvin for fungi; chloroquine and quinine as anti-malarialsMIC values of 100, 250, 125 μg/mL towards E. coli, S. aureus, and S. pyogenes and P. aeruginosa, respectively. MFC value of 250 μg/mL of C. albicans. MIC value of 100 μg/mL toward M. tuberculosis and of 0.29 μg/mL toward P. falciparumConjugated linoleic acid methyl ester, saturated FAME, steroids[63]
Quercus leucotrichophora, A. CamusG(+) bacteria: B. subtilis and S. aureus; G(-) bacteria: P. aeruginosa and E. coliDisk diffusion method for antibacterial susceptibility tests; MIC was tested in Mueller-Hinton broth for bacteria by two-fold serial dilution methodCiprofloxacinMIC: 0.125 mg/mL for B. subtilis and S. aureus; 0.5 mg/mL for P. aeruginosa and 1.0 mg/mL for E. coliFAME[56]
Quercus leucotrichophora A. CamusG(-) bacteria: E. coli MTCC-582 and P. aeruginosa MTCC-2295; G(+) bacteria: S. aureus MTCC-3160, B. subtilis MTCC-441 and S. pyogenes MTCC-1924Disk diffusion methodAmpicillinIZ of both extracts against all microorganisms: 8.53 ± 0.50 to 19.07 ± 0.31 mmFA; linoleic acid in stem bark and leaves extracts and cis-vaccenic acid in stem bark[81]
Vitex altissima L., V. negundo L. and V. trifolia L.Culex quinquefasciatus (early fourth-instar larvae)Larvicidal activity analyzed according to standard procedures (WHO-VBC 81.807, 1981)Not mentionedV. trifolia (LC50 = 9.26 ppm and LC90 = 21.28 ppm)FAME[64]
Linum usitatissimum L. A. flavus MTTC 2799 and A. ochraceus CECT 2092Determination of percent mycelial inhibition by growth radial technique on solid medium and by biomass technique on liquid mediumNot mentionedAntifungal index of FAME in solid medium: 54.19 ± 0.85 at 10 μL in A. flavus and 40.48 ± 0.12 at 90 μL for A. ochraceus at 90 μLFAME[57]
Scaphium macropodum (Miq.) Beumee ex. HeyneMycobacterium smegmatis, E. coli, S. typhimurium, B. subtilis, and S. aureusInhibitory activity of the extract by disk diffusion method; broth microdilution assay (MTT assay) was used to determine the MIC; MBC was determined via streak plate methodAmpicillin and rifampicinIZ of 10.67 ± 0.58 mm in S. aureus and of 9 mm in P. aeruginosa at 0.25 mg/mL. S. aureus showed the lowest MIC (0.78 mg/mL) and MBC (3.13 mg/mL). For M. smegmatis, MIC value was 3.13 mg/mL and MBC was 25 mg/mLMethyl hexadecanoate, hexadecanoic acid <n->[82]
Melastoma malabathricum L.S. aureus ATCC 25923, B. cereus ATCC 10876, P. aeruginosa ATCC 17853, S. typhi laboratory strainDisk diffusion methodRifampicinP. aeruginosa (9 mm at 0.25 mg/mL), S. aureus (7 mm, 1 mg/mL), S. typhi (9 mm at 1 mg/mL), B. cereus (10.5 mm at 2 mg/mL)Steryl glycoside:
β-sitosterol 3-O-β-D-glucopyranoside
[69]
Azadirachta indica A. JussMultidrug-resistant clinical isolates of S. aureus, Salmonella enterica serovar typhi, S. dysenteriae, E. coli, Vibrio cholerae, K. pneumoniae, and P. aeruginosaMIC determined by microbroth dilution method and antibacterial sensitivity of SQDG determined by disk diffusion method (CLSI protocol)Not mentionedMIC of 32 μg/mL for S. typhi and two isolates of S. dysenteriae; MIC of 64 μg/mL for three isolates of S. typhi, E. coli and V. cholerae and 256 μg/mL for K. pneumoniaeSQDG[71]
Azadirachta indica A. JussRaillietina spp. (helminth parasite)Ultrastructural changes by scanning electron microscopyPraziquantelAnthelmintic activity of SQDG with 0.5 and 1 mg/mL, respectively: paralysis time of 1 h and 0.7 h; death time of 1.6 h and 0.9 hSQDG[72]
Carapa guianensis and Carapa vasqueziiPhytopathogenic fungi: A. flavus, A. niger, and F. oxysporumFungal mycelial growth inhibition trials developed in 96-well microtiter plates adding 10 μL of conidia suspensions (2 × 105 conidia mL−1) and 90 μL yeast peptone dextrose. Inhibition of germination observed under light microscopy20 mM hydrogen peroxideMIC (μg/mL): 125–250 of C. guianensis and 15.6–125 of C. vasquezii against the three phytopathogenic fungiFA, FAME, squalene, β-sitosterol[58]
Ficus lutea Vahl Mucor miehei and B. subtilisDisk diffusion methodNystatinIZ of 17 mm for M. miehei; of 16 mm for B. subtilis; and of 12 mm for C. albicans exposed to 40 μg of compoundGlycosphingolipid [1-O-β-D-glucopyranosyl-(2S,3R,5E,12E)-2N-[(2′R)-hydroxyhexadecanoyl]-octadecasphinga-5,12-dienine] named lutaoside[76]
Ficus pandurata HanceYeast: C. albicans ATCC 90028, C. glabrata ATCC 90030, C. krusei ATCC 6258, A. fumigatus ATCC 90906, MRSA ATCC 33591, Cryptococcus neoformans ATCC 90113, S. aureus ATCC 2921, E. coli ATCC 35218, K. pneumoniae ATCC 13883, P. aeruginosa ATCC 27853, and Mycobacterium intracellulare ATCC 23068); chloroquine sensitive (D6, Sierra Leone) and resistant (W2, Indochina) strains of Plasmodium falciparum; parasite: Leishmania donovani promastigotesModified versions of the NCCLS methodsAntibacterial agent and antifungal agents not mentioned; antimalarial agents: chloroquine and artemisinin; anti-leishmanial agents: pentamidine and amphotericin BNo activity was observed for any compoundCeramides [panduramides A-D, and newbouldiamide][75]
Kunzea ericoides (A. Rich) J. ThompsonE. coli ATCC 25922 and S. aureus ATCC 25923Broth microdilution method utilizing the redox dye resazurinNot mentioned0.625–10 mg/mL for S. aureus and more than 10 mg/mL in E. coliSteryl esters, triacylglycerols, free FA, sterols and phospholipids[77]
Pentagonia gigantifolia DuckeC. albicans ATCC 90028 and fluconazole-resistant C. albicans strainsMIC and MFC determined by using a modified version of the microdilution NCCLS methods; sphingolipid reversal assayAmphotericin B, fluconazole and flucytosineC. albicans ATCC 90028 (0.52 to 1.04 μg/mL)Acetylenic acids: 6-octadecynoic acid and 6-nonadecynoic acid[38]
Hedyotis pilulifera (Pit.) T.N. Ninh S. aureus NBRC 100910, B. subtilis NBRC 13719, M. smegmatis NBRC 13167Microdilution methodAmpicillinOleanolic acid (MIC value of 2.5 μg/mL against M. smegmatis), rotungenic acid (MIC value of 2.5, 2.5, and 1.25 μg/mL against S. aureus, B. subtilis, and M. smegmatis, respectively), rotundic acid (MIC value of 5 μg/mL against B. subtilis)Triterpenoids, steroids, FA, glycolipids, and a ceramide[83]
Withania somnifera (L.) Dunal, Euphorbia hirta L., Terminalia chebula Retz.E. coli MTCC 46, P. aeruginosa MTCC 1934), Proteus mirabilis MTCC 3310, Raoultella planticola MTCC 2271, Enterobacter aerogenes (now Klebsiella aerogenes) MTCC 2822, B. subtilis MTCC 121, S. aureus MTCC 3160Disk diffusion method for antibiotic susceptibility testing. Broth microdilution method for determination of MIC valuesStreptomycinMIC: W. somnifera leaf (0.039 mg/mL on P. aeruginosa); T. chebula fruits and stems (0.039 mg/mL on E. coli) and T. chebula stems and fruits (0.039 mg/mL on S. aureus): MBC of 0.039 mg/mL of T. chebula bark on S. aureusSterols fraction[67]
Kaempferia pandurata Roxb. (synonym of Boesenbergia rotunda (L.) Mansf.) and Senna alata (L.) Roxb.MRSA, extended spectrum beta-lactamase (ESBL), and carbapenemase-resistant Enterobacteriaceae (CRE)Broth microdilution methodTetracycline and vancomycin for MRSA, cefotaxime and meropenem for ESBL-producing bacteria and for CREMIC: K. pandurata extract (256 μg/mL) and S. alata extract (512 μg/mL) against MRSASterols and triterpenoid[68]
Zygophyllum oxianum Boriss.S. aureus ATCC 29213 and B. subtilis ATCC 6059Modified disk diffusion methodAmpicillin, gentamicin sulfate, and nystatinMIC: 2-mg leaves and stems extract (8 mm in S. aureus and 6 mm in B. subtilis, weak antibacterial activity); 2 mg-BuOH extract of whole air-dried aerial organs extract (5 mm in B. subtilis, 4 mm in E. coli and 20 mm in C. maltosa, good antifungal activity)Total lipid extract from leaves, stems and aerial organs (hydrocarbons,
triterpenol and steryl esters, triacylglycerols, free FA, sterols, phospholipids)
[59]
Abbreviations: CLSI, Clinical and Laboratory Standards Institute (formerly NCCLS); CRE, carbapenemase-resistant Enterobacteriaceae; ESBL, extended-spectrum beta-lactamase; FA, fatty acid; FAME, fatty acid methyl ester; G(-), Gram-negative; G(+), Gram-positive; IC50, half maximal inhibitory concentration; IZ: inhibition zone; LC50, concentration (ppm) at which 50% of larvae showed mortality; LC90, concentration (ppm) at which 90% of larvae showed mortality; MBC, minimum bactericidal concentration; MFC, minimum fungicidal concentration; MIC, minimum inhibitory concentration; MIQ, minimum inhibition quantity; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (tetrazolium dye); NCCLS, National Committee for Clinical Laboratory Standards; ppm, parts per million; SQDG, sulfoquinovosyldiacylglycerol.
Table 3. Algae lipids and lipid-rich extracts with antimicrobial potential, their origin and extraction method.
Table 3. Algae lipids and lipid-rich extracts with antimicrobial potential, their origin and extraction method.
Scientific NameCollection SiteExtracting Solvent(s)/MethodIsolated Lipids or Lipid ClassesMethods for Compounds IdentificationRef.
Macroalgae–Chlorophyta
Caulerpa racemosaQionghai, Hainan, ChinaEtOH (95%). Extract partitioned with EtOAc and n-BuOHSQDG [2S-1,2-di-O-palmitoyl-3-O-(6’sulfo-α-D-quinovopyranosyl) glycerol]1H and 13C NMR, ESI-MS[95]
Caulerpa racemosa, Caulerpa lentilliferaPort Dickson, MalaysiaCHCl3, MeOHPUFA, MUFA, TerpenoidsLC-MS[96]
Caulerpa racemosa, Ulva fasciataBuzios, Rio de Janeiro, BrazilAcetone insoluble material extracted with CHCl3/MeOH (2:1 and 1:2, v/v). Lipid extract partitioned on SiO2 column, eluted with CHCl3, acetone or MeOHGlycolipid-rich extracts (Sulfoglycolipids, Glycosyldiacylglycerols)HPTLC[97]
Caulerpa spp., Chlorodesmis fastigiata, Halimeda spp., Penicillus capitatus, Penicillus dumentosus, Penicillus pyriformis, Rhipocephalus phoenix, Udotea argentea, Udotea cyathiformis, Udotea flabellum, Udotea petiolataBahamas, Florida Keys, Puerto Rico, Belize, Guan, Hawaii, Australia, Mediterranean SeaCH2Cl2. Chlorophylls removed with MgO3Si. Fractionation with SiO2 column and purification by HPLCSequiterpenoids, DiterpenoidsTLC, NMR, HPLC[98]
Chaetomorpha linumIMTA, Mar Piccolo of Taranto, ItalyCHCl3/MeOH (2:1, v/v), Soxhlet extractor, EtOH (95%)Lipid extracts1H and 13C NMR, 1D and 2D NMR, GC-FID, TLC[99]
Codium amplivesiculatumBahía Magdalena, MexicoCH2Cl2/EtOH (97:3, v/v). Liquid/liquid extraction CH2Cl2/H2O. Fractionation with CH2Cl2. Crystallization in hot MeOHFraction with clerosterol as main constituent. Isolated clerosterol did not show activity1H NMR, IR[100]
Ulva fasciataMalvan, IndiaEtOH, fractionated by neutral alumina column with EtOAc/MeOH Sphingosine (major component: N-palmitoyl-2-amino-1,3,4,5-tetrahydroxyoctadecane)1H and 13C NMR, FAB-MS, IR[101]
Malvan, IndiaEtOH (90%). Extract fractionated. n-hexane fraction chromatographed on SiO2 and flash SiO2Ceramide (Erythro-sphinga-4,8-dienine-N-palmitate)1H and 13C NMR, ESI-MS, GC-MS, IR[102]
Mediterranean Sea, EgyptCHCl3/MeOH (2:1, v/v). Glycolipid separation using acetone on SiO2 columnGlycolipid-rich extracts (DGDG)GC-FID, LC-MS/MS[103]
Mediterranean Sea, EgyptMeOH/CHCl3 (2:1, v/v). Sulfolipid isolation: diethylaminoethyl-cellulose column eluted with CHCl3/MeOH (6:4, v/v) and NH3Sulfolipids (SQDG)GC-MS, GC-FID, LC-MS/MS, IR[89]
Ulva rigidaCap Zebib and Ghar El Melh, TunisiaCH2Cl2 and CH2Cl2/MeOH (1:1, v/v). Extracts fractionated on SiO2 column and TLC with n-hexane/EtOAc/CH2Cl2/MeOHFA1H and 13C NMR, GC[27]
Macroalgae–Rhodophyta
Chondria armataGoa, West coast of India; Mumbai, IndiaMeOH and CHCl3, Polar fractions: petroleum ether/EtOAc (1:1, v/v), MeOH/CHCl3 (2:98, v/v), MeOH/CHCl3 (5:95, v/v)Neutral glycolipids [main compound MGDG(20:5/16:0)]1H and 13C NMR, ESI-MS/MS[104]
Chondrus crispus, Gracilaria vermiculophylla, Porphyra dioicaIMTA and Portuguese coast, PortugalEtOAc in Soxhlet extractorFAGC-FID[105]
Falkenbergia
(heteromorphic sporophyte of Asparagopsis taxiformis)
Kollam coast, IndiaMeOH. Fractionation on SiO2 column (petroleum ether/EtOAc and EtOAc/MeOH). Purification with TLC and RP HPLCFAGC-MS[106]
Galaxaura cylindrica, Laurencia papillosaRed Sea, EgyptCHCl3/MeOH (2:1, v/v). Glycolipid separation using acetone on SiO2 columnsGlycolipid-rich extracts
(DGDG)
LC-MS/MS[103]
Red Sea, EgyptMeOH/CHCl3 (2:1, v/v). Sulfolipid isolation: diethylaminoethyl-cellulose column (CHCl3/MeOH (6:4, v/v) and NH3)Sulfolipids (SQDG)GC-MS, GC-FID, LC-MS/MS, IR[89]
Gigartina tenellaSagami Bay, Kanagawa, JapanAcetone. Extract partitioned with EtOAc/H2O (3:1, v/v). Organic layer dissolved in EtOAc/MeOH/H2O (100:20:5, v/v) and chromatographed on SiO2 columnGlycolipid (Sulfolipids)1H and 13C NMR, HR-FAB-MS[107]
Gracilaria gracilisGanzirri lagoon and Margi channel, Eastern Sicily, ItalyCHCl3, Et2O in Soxhlet extractorFAGC-FID[94]
Gracilariopsis longissimaMar Piccolo of Taranto, ItalyCHCl3/MeOH/H2O (2:1:1, v/v)FA1H and 13C NMR, 1D and 2D NMR, GC-FID[108]
Hypnea musciformis, Osmundaria obtusiloba, Porphyra acanthophora, Pterocladiella capillaceaBuzios, Rio de Janeiro, BrazilAcetone insoluble material extracted with CHCl3/MeOH (2:1 and 1:2, v/v). Extract partitioned on SiO2 column (CHCl3, acetone or MeOH)Glycolipid-rich extracts (Sulfolipids, Glycosyldiacylglycerols)HPTLC[97]
Jania corniculata, Laurencia papillosaSuez Canal, EgyptEtOH (70%), CH2Cl2FAGC-MS[93]
Laurencia okamuraiNanji Island in the East China Sea, Zhejiang Province, ChinaEtOH (95%) extract partitioned with Et2O and fractionated by SiO2 (gradient system: petroleum ether –CH2Cl2 (10:0 → 1:9)), Sephadex column, and purification by semi-preparative C18 HPLC FA ethyl esters [(9Z,12Z,15Z,18Z,21Z)-ethyl tetracosa-9,12,15,18,21-Pentaenoate, (10Z,13Z)-ethyl nonadeca-10,13-dienoate, (9Z,12Z)-ethyl nonadeca-9,12-dienoate, (Z)-ethyl octadec-13-enoate (4), and (Z)-ethyl hexadec-11-enoate]1H and 13C NMR, 1D and 2D NMR, IR, HR-EI-MS[109]
Laurencia spp.Pulau Tioman, Pahang, Pulau Karah, Terengganu, Pulau Nyireh, Terengganu, MalaysiaMeOH. Extract partitioned with Et2O and H2O and fractionated by SiO2 column (hexane/EtOAc)Sesquiterpenes (Halogenated sesquiterpenes)1H and 13C NMR, LREIMS, HREIMS[110]
Osmundaria obtusilobaBuzios, Rio de Janeiro, BrazilAcetone insoluble material extracted with CHCl3/MeOH (2:1 and 1:2, v/v). Extract partitioned (CHCl3/MeOH/0.75% KCl (8:4:3, v/v)). Fractionation on SiO2 column (CHCl3, acetone and MeOH). MeOH fraction purified on SiO2 column (CHCl3/MeOH, 90:10, v/v)Glycolipids (Sulfoglycolipids)1H and 13C NMR, ESI-MS/MS[111]
Palmaria palmata, Grateloupia turuturuBatz-sur-Mer, FranceCH2Cl2/MeOH (2:1, v/v), MeOH/H2O (1:1, v/v)Polar lipids1H and 13C NMR[112]
Pyropia orbicularisMaitencillo, ChileMeOH, acetone, CH2Cl2, n-hexane. Soxhlet extractor. n-hexane extract fractionated on SiO2 column (2, 10, 20, 30 and 100% acetone)Phospholipids (main compounds PC-O, PE, PS, PI, SM, GlCer), Glycolipids (MGDG), Triacylglycerol, DAGLC-ESI-MS/MS[113]
Sphaerococcus coronopifoliusAtlantic coast of MoroccoMeOH/CH2Cl2. Extract separated on SiO2 column (hexane, gradients of hexane/CH2Cl2 and CH2Cl2/acetone, and MeOH)Bromoditerpenes (Sphaerolabdadiene-3,14-diol (1), Sphaerococcenol)1H and 13C NMR, HRMS, EIMS, CIMS, FTIR, UV[114]
Macroalgae–Ochrophyta
Dictyota cervicornis, Dictyota menstrualisBuzios, Rio de Janeiro, BrazilAcetone insoluble material extracted with CHCl3/MeOH (2:1 and 1:2, v/v). Extract partitioned on SiO2 column (CHCl3, acetone or MeOH)Glycolipid-rich extracts (Sulfoglycolipids, Glycosyldiacylglycerols)HPTLC[97]
Dictyota fasciola, Taonia atomaria
Mediterranean Sea, EgyptCHCl3/MeOH (2:1, v/v). Glycolipid separation using acetone on SiO2 columnGlycolipid-rich extracts (DGDG)GC-FID, LC-MS/MS[103]
Mediterranean Sea, EgyptMeOH/CHCl3 (2:1, v/v). Sulfolipid isolation: diethylaminoethyl-cellulose column (CHCl3/MeOH (6:4, v/v) and NH3)Glycolipids (Sulfolipids)GC-MS, GC-FID, LC-MS/MS, IR[89]
Fucus evanescensWest coast of Ungava Bay, CanadaEtOAc (99%), CH2Cl2. EtOAc algal extract acetylated and organic layer purified by flash chromatography (0% → 50% EtOAc in hexane and flushed with 100% EtOAc and 5% MeOH in 95% EtOAc)Glycolipid-rich extracts1H and 13C NMR[115]
Himanthalia elongataLas Palmas, SpainPressurized liquid extraction Hexane, EtOH, H2OSterol (Fucosterol), FAGC-MS, HPLC-DAD[116]
Laminaria cichorioidesKhasan region of the Primorskii Territory, in the Troitsa Gulf (the Sea of Japan), RussiaEtOH (96%). Lipophilic fraction extracted with CHCl3. Fractionation of lipid classes on SiO2 columnGlycolipids (MGDG, DGDG, SQDG), Free FA, PUFA [91]
Sargassum dentifoliumSuez Canal, EgyptEtOH (70%), CH2Cl2FAGC-MS[93]
Sargassum fusiforme, Sargassum vulgareRed Sea, EgyptEt2O, MeOH, EtOH, CHCl3Terpenoids, FAGC-MS[117]
Sargassum pallidumTrinity Bay in the Peter the Great Gulf, RussiaEtOH; EtOH/acetone (1:1, v/v), EtOH/CHCl3 (1:1, v/v). Fractionation of lipid classes on SiO2 column (hexane, Et2O/hexane with increasing ether concentration (95:5 → 50:50, v/v) and CHCl3)Glycolipids (MGDG, SQDG; DGDG), Free FA/Esters, Triacylglycerols, DAG [118]
Sargassum vulgareSepetiba Bay, BrazilCHCl3/MeOH (2:1 and 1:2, v/v). Fractionated on SiO2 column (CHCl3, acetone and MeOH)Glycolipid-rich extracts (Sulfoglycolipids)1H and 13C NMR, ESI-MS-MS[119]
Sargassum wightiiGulf of Mannar, IndiaMeOH. Isolation on SiO2 column (hexane/EtOAc, EtOAc/MeOH). Purification on flash SiO2 column (CHCl3/MeOH gradients)Glycolipid (Sulfoglycerolipid, 1-O-palmitoyl-3-O(6′-sulfo-α-quinovopyranosyl)-glycerol)1H and 13C NMR, IR[120]
Microalgae
Chaetoceros muelleri Supercritical fluid extraction, EtOH (99.5%)Triacylglycerol, DAG, MAG, sterols (cholesterol), FAHPLC-ELSD, GC-FID[121]
Chlorococcum HS-101JapanMeOH extract, partitioned with hexane. SiO2 column (MeOH/CHCl3 gradient). Active fraction recovered with MeOH/CHCl3 (5:95, v/v)FA1H and 13C NMR, GC-MS[122]
Dunaliella salinaJerusalem, IsraelPressurized liquid extracts: hexane, petroleum ether, EtOHFA
Sesquiterpenoids (Neophytadiene), Diterpenoid (Phytol)
GC-MS[123]
Navicula delogneiLepreau Ledges, New Brunswick, CanadaMeOH, CHCl3, extract chromatographed on SiO2 column (CHCl3 and CHCl3/MeOH)FA [(6Z,9Z,12Z,15Z)-hexadecatetraenoic acid, (6Z,9Z,12Z,15Z)-octadecatetraenoic acid), Ester ((E)-phytol (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate]1H and 13C NMR, GC-MS[124]
Phaeodactylum tricornutumExperimental Phycology and Culture Collection of Algae at the University of Göttingen (Germany)EtOAc and MeOH extracts applied to SiO2 Sep Pak cartridges. EtOAc extract eluted with 10% step increases of hexane/EtOAc until 100% EtOAc. MeOH extract eluted with 10% step increases of EtOAc/MeOH until 100% MeOH Free FA (palmitoleic acid, HTA) 1H and 13C NMR, ESI-MS[125]
MeOH/H2O (5:1, v/v). Extract redissolved in MeOH (70%) and fractioned on Sep Pak cartridge (MeOH (70%) followed by constant volumes of MeOH (5% steps → 100%)). Fractionated by RP HPLC FA (EPA) 1H NMR, ESI-MS[126]
Synechocystis sp.Las Palmas, SpainPressurized liquid extraction: hexane, EtOH, H2OFA, Sesquiterpenoids (Neophytadiene)GC-MS, HPLC-DAD[116]
Table 4. Antimicrobial activity of algae lipids or algae lipid-rich extracts.
Table 4. Antimicrobial activity of algae lipids or algae lipid-rich extracts.
Scientific NameAntimicrobial ActivityTested MicroorganismsAntimicrobial Testing Method/EvaluationReference Antimicrobial (Positive Control)MIC, MBC, Diameter of Inhibition Zone (IZ, in mm) or OtherRef.
Macroalgae–Chlorophyta
Caulerpa racemosa Antiviral Viruses: Cox B3, HSVCytopathic effect (CPE) reduction assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methodAcyclovir (HSV), Ribavirin (Cox B3)IC50/CC50 (µg/mL)/SI
Cox B3: 31.3/500/16
HSV: 7.9/250
[95]
Caulerpa racemosa, Caulerpa lentilliferaAntibacterial G(+):MRSA (MTCC 381123)
G(-): E. coli K1 (MTCC 710859)
Disk diffusion method, crude extracts (CHCl3 and MeOH)Penicillin-streptomycinPI: 97.7% (C. racemosa)[96]
Caulerpa racemosa, Ulva fasciata Antiviral Viruses: HSV-1-ACVs, HSV-1-ACVr Titer reduction [97]
Caulerpa spp., Chlorodesmis fastigiata, Halimeda spp., Penicillus capitatus, Penicillus dumentosus, Penicillus pyriformis, Rhipocephalus phoenix, Udotea argentea, Udotea cyathiformis, Udotea flabellum, Udotea petiolataAntibacterial, AntifungalG(-):Serratia marinoruba, Vibrio splendida, V. harveyi, V. leiognathi, Vibrio sp.
Undescribed bacteria: VJP Cal8101, VJP Cal8102, VJP Cal8103
Fungi: Leptosphaeria sp. Lulworthia sp., Alternaria sp., Dreschleria haloides, Lindra thallasiae,
Undescribed fungi: VJP Cal8104, VJP Cal8105
Plate assay-disk method IZ (mm) > 2[98]
Chaetomorpha linumAntibacterialG(+): Pseudomonas sp., Staphylococcus sp., Streptococcus agalactiae, Enterococcus sp.
G(-): Vibrio alginolyticus, V. harveyi, V. mediterranei, V. ordalii, V. parahaemolyticus, V. salmonicida, V. vulnificus
Yeast: C. albicans,
Candida famata, C. glabrata
Disk diffusion method IZ (mm)
V. ordalii: 8–12
V. vulnificus: 8–12
[99]
Codium amplivesiculatumAntibacterialG(+): S. aureus (ATCC BAA-42, resistant to methicillin, penicillin, ampicillin/sulbactam, oxacillin, cefalotine)
G(-): V. parahaemolyticus (17802)
Disk diffusion method MIC (µg/mL)/IZ (mm)
S. aureus: 125/15
V. parahaemolyticus: >250/8
[100]
Ulva fasciata Antiviral Virus: Semeliki Forest Virus (SFV) 20 mg/mouse/7 days by giving 50% protection[101]
Antiviral Viruses: Japanese encephalitis
virus (JEV), encephalomyocarditis (EMC) virus
96-well microtiter plates CC50 (µg/mL)/EC50 (µg/mL)/TI
JEV: 7.8/3.9/2.0
[102]
Antifungal, Antiviral Yeast: C. albicans;
Fungus: A. niger
Virus: HSV-1
Disk diffusion method; plaque reduction assay (antiviral) MIC (µg/mL)/IZ (mm)
C. albicans: 60/8,
A. niger: 80/13
HSV-1: 9.37–15.62%
[103]
Antibacterial, AntiviralG(+):B. subtilis RRL B-94
G(-): E. coli NRRL B-3703
Virus: HSV-1
Disk diffusion methodChloramphenicol (bacteria), Acyclovir (virus)MIC (µg/mL)/IZ (mm)
PI(%)
E. coli: 60/13
B. subtilis: 40/16
HSV-1: 18.75–46.87%
[89]
Ulva rigidaAntibacterial G(+): S. agalactiae, S. aureus (ATCC 25923), S. aureus (ATCC 6538), E. faecalis (ATCC 29212), Micrococcus sp.
G(-): Vibrio tapetis (CECT4600), V. anguillarum (ATCC 12964T), V. alginolyticus (ATCC 17749T), E. coli O126-B16 (ATTC 14948), E. coli (ATCC 25922), E. coli (ATCC 8739), Pseudomonas cepacia, P. fluorescens (AH2), P. aeruginosa (ATCC 27853), Aeromonas salmonicida (LMG3780), A. hydrophila B3, S. typhimurium (C52)
Yeast: C. albicans (ATCC10231)
Disk diffusion method and broth microdilution technique IZ (mm)
6.3–16.3
[27]
Macroalgae–Rhodophyta
Chondria armataAntibacterial, AntifungalG(+): S. aureus
G(-): E. coli, P. aeruginosa, S. typhi, Salmonella flexneri, Klebsiella sp., V. cholerae
Yeast: C. albicans, C. neoformans, Rhodotorula sp.
Fungi: Aspergillus fumigatus, A. niger
Disk diffusion methodStreptomycin,
Nystatin
1 < IZ ≤ 4[104]
Chondrus crispus, Gracilaria vermiculophylla, Porphyra dioicaAntibacterial, AntifungalG(+): Listeria innocua (NCTC 11286), B. cereus (ATCC 11778), E. faecalis (LMG S 19456 5002), Lactobacillus brevis (LMG 6906), S. aureus (ATCC 6538), MRSA
G(-): E. coli (ATCC 8739), Salmonella enteritidis (ATCC 3076), P. aeruginosa (ATTC 10145)
Yeast: Candida spp. (CCUG 49242)
Disk diffusion methodAmpicillin (L. innocua), Cycloheximide (Candida spp.), Chloramphenicol (other microorganisms)IZ (mm)
C. crispus: 5 < IZ ≤ 20
G. vermiculophylla: 10 < IZ ≤ 15
P. dioica: 5 < IZ ≤ 12
[105]
Falkenbergia
(heteromorphic sporophyte of Asparagopsis taxiformis)
AntibacterialG(+): S. epidermidis, S. aureus, B. subtilis
G(-): V. vulnificus (MTCC 1145), V. parahaemolyticus (MTCC 451), V. harveyi (MTCC 3438), V. alginolyticus (MTCC 4439), V. alcaligenes (MTCC 4442), P. aeruginosa, K. pneumoniae
Broth dilution methodChloramphenicol, Nalidixic acidIZ (mm)/MIC (µg)/MBC (µg)
S. epidermidis: 21/1250/270
S. aureus: 21/750/170
B. subtilis: 23/750/180
V. vulnificus: 31/750/90
V. parahaemolyticus: 28/750/110
V. harveyi: 26/750/60
V. alginolyticus: 32/500/80
V. alcaligenes: 33/500/50
P. aeruginosa: 19/1250/420
K. pneumoniae: 15/1250/380
[106]
Galaxaura cylindrica, Laurencia papillosaAntiviral Virus: HSV-1 Plaque reduction assayAcyclovirInhibition (%)
L. papillosa: 9.37–31.25
G. cylindrica: 15.62–28.12
[103]
Antibacterial, AntiviralG(+): B. subtilis NRRL B-94
G(-): E. coli NRRL B-3703
Virus: (HSV-1)
Disk diffusion methodChloramphenicol (bacteria), Acyclovir (virus)MIC (µg/mL)/IZ (mm)
PI(%)
L. papillosa
E. coli: -/8
B. subtilis: -/11
HSV-1: 40.62–59.37%
G. cylindrica
E. coli: 80/11
B. subtilis: 80/11
HSV-1: 45.87–59.37%
[89]
Gigartina tenellaAntiviralHIV-reverse transcriptase type 1 IC50 11.2 µM[107]
Gracilaria gracilisAntibacterialG(+): B. subtilis
G(-): V. fischeri, V. cholerae, P. aeruginosa, Salmonella sp., A. hydrophila
Disk diffusion methodChloramphenicolMIC: 5 µg/disk
IZ (mm)
B. subtilis 10.3–17.6 (CHCl3)/10–15.6 (Et2O)
[94]
Gracilariopsis longissimaAntibacterial, AntifungalG(+): S. agalactiae, Enterococcus sp.
G(-): P. aeruginosa, V. salmonicida, V. fluvialis, V. vulnificus, V. cholerae non-O1, V. alginolyticus
Yeast: C. albicans, C. famata, C. glabrata
Disk diffusion method IZ (mm)
V. alginolyticus: 25
V. fluvialis: 8
V. vulnificus: 15
V. cholerae non-O-1:10
[108]
Hypnea musciformis, Osmundaria obtusiloba, Porphyra acanthophora, Pterocladiella capillacea Antiviral Virus: HSV-1-ACVs, HSV-1-ACVr Titer reduction PI(%)/VII
O. obtusiloba
ACVs-HSV-1: 82.2–99.5/0.75–2.35
HSV-1-ACVr: 99.7–99.9/2.5–4.5
[97]
Jania corniculata, Laurencia papillosaAntibacterial, AntifungalG(+): B. subtilis, Staphylococcus albus, E. faecalis
G(-): E. coli
Yeast: C. albicans
Fungus: A. flavus
Disk diffusion method 11 < IZ ≤ 15
No IZ (A. flavus)
[93]
Laurencia okamuraiAntifungalYeast: C.
neoformans (32609), C. glabrata (537)
Fungi: Trichophyton rubrum (Cmccftla), A. fumigatus (07544)
Broth dilution methodAmphotericin B, fluconazole, voriconazole, ketoconazoleMIC80 (µg/mL)
C. neoformans: 8–64
C. glabrata: 4–64
A. fumigatus: >64
T. rubrum: 64
[109]
Laurencia spp. Antibacterial G(-): Chromobacterium violaceum, P. mirabilis,
P. vulgaris, Erwinia sp.,
V. parahaemolyticus, V. alginolyticus
Disk diffusion method MIC (µg/disk)
C. violaceum: 10–40
P. mirabilis: 20–40
P. vulgaris: 20–40
Erwinia sp.: 10–30
V. parahaemolyticus: 20–40
V. alginolyticus: 20–30
[110]
Osmundaria obtusiloba Antiviral Virus: HSV-1, HSV-2 Titer reductionAcyclovirEC50 (µg/mL)/SI/PI(%)
HSV-1: 42/1.7/75
HSV-2: 12/6/96
[111]
Palmaria palmata, Grateloupia turuturuAntibacterialG(-): V. harveyi ORM4 Broth microdilution method 0.2 < PI ≤ 7.9%[112]
Pyropia orbicularisAntibacterialG( + ): S. aureus, B. cereus
G(-): E. coli
Disk diffusion methodKanamycin16 < IZ < 26[113]
Sphaerococcus coronopifoliusAntibacterial, AntiplasmodialG(+): S. aureus (ATCC # 6538)
Parasitic protozoa: P. falsciparum (FCB1)
Antibacterial: Disk-diffusion, Antimalarial: inhibition of [3H]-hypoxanthine uptake by P. falsciparum cultured in human blood S. aureus-MIC: 0.104–0–146 µM
P. falciparum-IC50: 1 µM
[114]
Macroalgae–Ochrophyta
Dictyota cervicornis, Dictyota menstrualis Antiviral Virus: HSV-1-ACVs, HSV-1-ACVr Titer reduction [97]
Dictyota fasciola, Taonia atomariaAntibacterial, Antifungal, Antiviral G(+): B. subtilis
G(-): E. coli
Fungi: C. albicans, A. niger
Virus: HSV-1
Disk diffusion method (antibacterial); Plaque reduction assay (antiviral)
D. fasciola:
Inhibition (%)
HSV-1: 50.00–81.25%
T. atomaria: MIC (µm/mL)/IZ(mm)
B. subtilis: 80/9, E. coli: 80/7, C. albicans: 80/10,
A. niger: 60/12
Inhibition (%)
HSV-1: 31.25–34.37%
[103]
Antibacterial, AntiviralG(+):B. subtilis NRRL B-94
G(-): E. coli NRRL B-3703
Virus: HSV-1
Disk diffusion method (antibacterial); Plaque reduction assay (antiviral)Chloramphenicol (bacteria), Acyclovir (virus)MIC (µg/mL)/IZ (mm)
PI(%)
D. fasciola
E. coli: -/8
B. subtilis: -/10
HSV-1: 46.87–70.12%
T. atomaria:
E. coli: 60/15
B. subtilis: 40/13
HSV-1: 43.75–56.25%
[89]
Fucus evanescensAntibacterialG(+): B. cereus, Clostridium difficile, MRSA, Propionibacterium acnes (ATCC and clinical isolate), S. pyogenes
G(-): Acinetobacter baumannii, E. coli, Haemophilus influenzae, K. pneumoniae, Legionella pneumophila, P. aeruginosa
Disk diffusion method MIC100: 50 µg/mL[115]
Himanthalia elongataAntibacterialG(+): S. aureus ATCC 25923,
G(-): E. coli ATCC 11775
Yeast: C. albicans ATCC 60193
Fungi: A. niger ATCC 16404
Broth microdilution method MBC (mg/mL)
S. aureus: 6.25
E. coli: 6.00
MFC (mg/mL)
C. albicans: 8
A. niger: 12
[116]
Laminaria cichorioidesAntibacterial, AntifungalG(+): S. aureus ATCC 21027
G(-): E. coli ATCC 15034
Yeast: Safale S04, C. albicans KMM 455
Fungi: A. niger KMM 4634, F. oxysporum KMM 4639
Disk diffusion methodFucoxanthin, NitrofunginIZ (mm)
S. aureus: 2–5
E. coli:1–6
C. albicans: 1–6
A. niger: 1–3
F. oxysporum: 1–4
[91]
Sargassum dentifoliumAntibacterial, AntifungalG(+): B. subtilis, S. albus, E. faecalis
G(-): E. coli
Yeast: C. albicans
Fungus: A. flavus
Disk diffusion method 11 < IZ (mm) ≤ 12
No IZ (A. flavus)
[93]
Sargassum fusiforme, Sargassum vulgareAntibacterialMultidrug resistant:
S. aureus,
P. aeruginosa,
Shigella flexneri,
E. coli,
Corynebacterium sp.
Agar well diffusion 9.33 < IZ (mm) ≤ 23.33
MIC: 50–100 mg/mL
[117]
Sargassum pallidumAntibacterial, AntifungalG(+): S. aureus ATCC 21027
G(-): E. coli ATCC 15034
Yeast: C. albicans KMM 455
Fungi: A. niger KMM 4634, F. oxysporum KMM 4639, Septoria glycines
Agar well diffusion IZ (mm)
S. aureus: 0.7–14.5
E. coli: 0.5–6.7
C. albicans: 1.0–4.5
A. niger: 2.0–5.7
F. oxysporum: 1.0–5.2
S. glycines: 2.0–5.7
[118]
Sargassum vulgareAntiviralVirus: HSV-1, HSV-2Titer reductionAcyclovirPI (%)
HSV-1: 96.0–99.9
HSV-2: 99.9
[119]
Sargassum wightii Antibacterial Xanthomonas oryzae pv. oryzae CAS ar01Disk diffusion method IZ (mm): 3.0–13.5[120]
Microalgae
Chaetoceros muelleriAntibacterial, AntifungalG(+): Staphyloccocus aureus (ATCC 25923)
G(-):E. coli (ATCC 11775)
Yeast: C. albicans (ATCC 60193)
Broth microdilution method Chloramphenicol, Amphotericin B MBC (mg/mL)
E. coli: 12–15
S. aureus: 12–17
C. albicans: 7–9
[121]
Chlorococcum HS-101AntibacterialG(+): MRSA, S. aureus ATCC 25923Disk diffusion methodGentamicin, Amikacin, Cephalosporin, Habekacin, Ampicillin, Vancomycin, Oxytetracyclin, Erythromycin, Cefmetazole, Fosfomycin, Imipenem, MinomycinIZ (mm): 18.7–28.3[122]
Dunaliella salinaAntibacterial, AntifungalG(+): S. aureus ATCC 25923
G(-): E. coli ATCC 11775
Yeast: C. albicans ATCC 60193
Fungi: A. niger ATCC 16404
Disk diffusion methodChloramphenicol (bacteria),
Amphotericin B (yeast and fungi)
MBC (mg/mL)
E. coli: 6–30
S. aureus: 8–30
MFC (mg/mL)
C. albicans: 12–30
A. niger: 32–>35
[123]
Navicula delognei f. ellipticaAntibacterialG(+): Staphyloccus aureus (ATCC 25923), S. epidermidis (ATCC 12228)
G(-): S. typhimurium (ATCC 14028), P. vulgaris (ATCC 13315), Enterobacter cloacae (ATCC 23355), E. coli (ATCC 25922), K. pneumoniae (ATCC 13883), Serratia marcescens (ATCC 8100)
Disk diffusion method Ampicillin, Tetracycline, Chloramphenicol IZ (mm)
S. aureus >4
S. typhimurium >4
S. epidermidis >2
P. vulgaris >2
E. coli IZ noticeable
No IZ (E. cloacae, K. pneumoniae, S. marcescens)
[124]
Phaeodactylum tricornutumAntibacterial, AntifungalG(+):
S. aureus
(SH1000), Bacillus weihenstephanensis
(10390), MRSA 252, MRSA 16a, S.
epidermidis, M. luteus (NCIMB 9278), Planococcus citreus
(NCIMB 1493), B. cereus (883-00)
G(-): Alteromonas
haloplanktis (NCIMB 19), A. hydrophila
(NCIMB 1108), Photobacterium
phosphoreum (NCIMB 64), Psychrobacter immobilis (NCIMB 308), Listonella anguillarum
(MT1637),
E. coli B,
P. aeruginosa (NCIMB 10775)
Yeast: C. glabrata, Candida neoformis,
Candida sp., Saccharomyces cerevisiae BY4741a
Disk diffusion method Ampicillin IC50 (µM)/MBC (µM)
S. aureus: 10–40/40–80
[125]
Antibacterial, AntifungalG(+):M. luteus (NCIMB 9278), Planococcus
citreus (NCIMB 1493), B. cereus (883-00), S. aureus (SH1000), B. weihenstephanensis (10390), MRSA 252, MRSA16a, S. epidermidis
G(-): Alteromonas haloplanktis (NCIMB 19), A. hydrophila (NCIMB 1108), Photobacterium phosphoreum (NCIMB 64), Psychrobacter immobilis (NCIMB308), Listonella anguillarum (MT1637), E. coli B, P. aeruginosa (NCIMB 10775)
Yeast:C. glabrata, C. neoformis, Candida sp., S. cerevisiae BY4741a
Agar well diffusion Growth inhibition (mm2)
≤50–>50
S. aureus: 25–190 mm2
[126]
Synechocystis sp.AntibacterialG(+): S. aureus ATCC 25923
G(+): E. coli ATCC 11775,
Yeast: C. albicans ATCC 60193
Fungi: A. niger ATCC 16404
Broth microdilution method MBC (mg/mL)
S. aureus: 7
E. coli: 5.6
MFC (mg/mL)
C. albicans: 12
A. niger: 14
[116]
Abbreviations: CC: cytotoxic concentration; EC: effective concentration; HSV: herpes simplex virus; IC: inhibitory concentration; IZ: inhibition zone; MIC: minimum inhibitory concentration; MBC: minimum bactericidal concentration; MFC: minimum fungicidal concentration; MRSA: methycillin-resistant Staphylococcus aureus; PI: percentage of inhibition; SI: selectivity index; TI: therapeutic index; VII: viral inhibition index.
Table 5. Marine invertebrate lipids or lipid-rich extracts with antimicrobial potential, their origin and extraction method.
Table 5. Marine invertebrate lipids or lipid-rich extracts with antimicrobial potential, their origin and extraction method.
Scientific NamePhylum
(Class)
Collection SiteExtracting Solvent(s)/MethodIsolated Lipids or Lipid ClassesCompound Identification MethodsRef.
Acanthodendrilla sp.Porifera (Demospongiae)Gokasho Bay, Tokyo, JapanMeOH. Aqueous residue extracted with Et2O and n-BuOH. Organic extract fractionated by SiO2 (MeOH/CHCl3), purified by ODS column and C18 RP HPLCSteroid sulfates1H and 13C NMR[169]
Porifera (Demospongiae)Kundingarengkeke
Island, Indonesia
EtOH, acetone and MeOH. Crude extract partitioned between aqueous MeOH and hexane, EtOAc, and BuOH. Hexane extract fractionated on normal-phase SiO2 column (n-hexane/EtOAc, 7:3, v/v). Purification by semi-preparative HPLCSesterterpenes
(Luffariellolide derivatives, Acantholides)
1H and 13C NMR, ESI-MS, HR-EI-MS[190]
Agelas oroidesPorifera (Demospongiae)Gökçeada, Northern Aegean Sea,
Turkey
MeOH, MeOH/CHCl3 (1:1, v/v) and CHCl3. Extract dissolved in MeOH/H2O (9:1, v/v) partitioned against n-hexane. n-hexane, CH3Cl and MeOH extracts fractionated on SiO2 (EtOAc (0 → 100%) in hexane). Sephadex LH20 and C18 flash columnFA1H and 13C NMR, 1D and 2D NMR, GC-MS, ESI-MS[162]
Caminus sphaeroconia
Porifera (Demospongiae)
DominicaMeOH extracts chromatographed on Sepahdex LH 20 (MeOH and EtOAc/MeOH/H2O 20:5:2). Purification by gradient on SiO2 (CH2Cl2 to CH2Cl2/MeOH 9:1, v/v)Glycolipid (Caminoside)1H and 13C NMR, ESI-MS[147]
DominicaMeOH extract purified by Sephadex LH-20 (MeOH). Sephadex LH-20 (EtOAc/MeOH/H2O (20:5:2, v/v))Glycolipid (Caminoside)1H and 13C NMR, ESI-MS[176]
Dysidea arenariaPorifera (Demospongiae)Hainan Island, South China Sea, ChinaCHCl3-soluble portion was repartitioned between petroleum ether and 90% MeOH. MeOH extract on flash SiO2 column (ether/EtOAc gradient)Sesquiterpenoid
(Sesquiterpenoid hydroquinone)
1H and 13C-NMR, ESI-MS[184]
Dysidea sp.Porifera (Demospongiae)Lakshadweep Islands, Kerala, IndiaEtOAc and MeOH. EtOAc extract chromatographed on Sephadex LH20 (MeOH/CHCl3, 1:1, v/v), SiO2 (2% EtOAc petroleum ether)Sesterterpenes
(Sesterterpene sulfates)
1H and 13C NMR, HR-FAB-MS[183]
Erylus lendenfeldiPorifera (Demospongiae)Gulf of Eilat, Red SeaMeOH/CHCl3, RP on a C18 column (decreasing percentage of H2O in MeOH)Steroidal glycoside
(Eryloside)
1H and 13C NMR, UV, IR[172]
Erylus placentaPorifera (Demospongiae)Hachijo Island, Japann-PrOH/H2O (3:1, v/v). Extracts partitioned between H2O and CHCl3. H2O layer partitioned between n-BuOH and H2O. BuOH fraction separated by C18 flash (n-PrOH/H2O (1:9, 3:7, 5:5, and 8:2, v/v) and CHCl3/MeOH/H2O(6:4:1, v/v))Steroidal glycoside
(Sokodosides)
1H and 13C NMR, GC-FID, UV[174]
Euryspongia sp.Porifera (Demospongiae)Light House Reef, Koror, PalauMeOH. Extracts fractionated by HP20SS column (acetone/H2O)Steroid sulfates (Eurysterols)1H and 13C NMR, ESI-MS, UV, IR[167]
Fasciospongia sp.Porifera (Demospongiae)Cape Leeuwin, Western AustraliaEtOH extract partitioned into n-BuOH and H2O soluble fractions. n-BuOH fraction subsequently defatted by sequential trituration in n-hexane and CH2Cl2 soluble fractions. CH2Cl2 fractions subjected to SPE or HLPCMeroterpene
(Meroterpene sulfate fascioquinol)
1H and 13C NMR, HR-ESI-MS, UV[186]
Halichondria sp.
Porifera (Demospongiae)Unten Port, Okinawa, JapanMethanolic extract partitioned between H2O and EtOAc. EtOAc soluble material subjected to SiO2 column (CHCl3/MeOH, (95:5, v/v) and petroleum ether/Et2O (9:1, v/v))Sesquiterpenoids
(Halichonadins)
1H and 13C NMR, EI-MS, IR[187]
Porifera (Demospongiae) MeOH extract partitioned between H2O and EtOAc. EtOAc-soluble material subjected to SiO2 column (n-hexane/EtOAc, 1:1 → MeOH). MeOH fraction subjected to SiO2 column (CHCl3/MeOH, 95:5 → 7:3). CHCl3/MeOH (7:3) fraction separated on SiO2 column (EtOAc/MeOH, 5:1 → MeOH)Sesquiterpenoid
(Halichonadins)
1H and 13C NMR, ESI-MS, HR-ESI-MS, IR[188]
Haliclona simulansPorifera (Demospongiae)Kilkieran Bay, Galway, IrelandAcetone and MeOH extracts subjected to HP20 chromatography (100% H2O → 100% MeOH). Fractionated on flash forward system. SiO2 column (100% hexane → 100% EtOAc)Steroids
(24-vinyl-cholest-9-ene-3β,24-diol, 20-methyl-pregn-6-en-3β-ol,5α,8α-epidioxy, 24-methylenecholesterol)
1H- and 13C NMR, GC-MS[170]
Jaspis stelliferaPorifera (Demospongiae)Ishigaki Island, Okinawa, JapanMeOH. EtOAc soluble material subjected to SiO2 column (CHCI3/MeOH, 9:1 and hexane/EtOAc, 3:7, v/v). EtOAc-soluble material subjected to SiO2 columns and C18 HPLCNortriterpenoids
(Jaspiferals)
1H and 13C NMR, EI-MS, UV, IR[181]
Luffariella geometricaPorifera (Demospongiae)Great Australian Bight, AustraliaCH2Cl2. Sequential fractionation to obtain pure compoundsSesterterpenes
(Luffarins)
1H and 13C NMR, EI-MS, UV, IR[178]
Luffariella variabilis
Porifera (Demospongiae)Western Carolines, PalauCH₂Cl₂, purified by chromatographySesterterpenoids
(Manoalide)
1H and 13C NMR, UV, IR[180]
Western Carolines, PalauCH₂Cl₂, purified by chromatographySesterterpenoids
(Manoalides)
1H and 13C NMR, UV, IR[179]
Melophlus sarasinorumPorifera (Demospongiae)Makassar, Sulawesi Island, IndonesiaAcetone and MeOH. Extract partitioned between EtOAc and H2O. Aqueous extract on HP20 (MeOH, H2O). MeOH eluate on C18 (MeOH and H2O, gradient elution)Steroidal glycosides
(Sarasinoside)
1H and 13C NMR, HR-ESI-MS, LC-MS, UV
[173]
Oceanapia sp.Porifera (Demospongiae)Kamagi Bay, Sada Peninsula, JapanMeOH extracts partitioned between ether and H2O. Organic phase partitioned between n-hexane and MeOH/H2O (9:1, v/v). Aqueous MeOH fraction subjected to C18. Purification on SiO2 column (CHCl3, CHCl3/MeOH (9:1), CHCl3/MeOH/H2O (6:4:1), and MeOH)Acetylenic acid1H and 13C NMR, FAB-MS, UV, IR[161]
Paragrantia cf. waguensisPorifera (Calcarea)Onna village, Okinawa, JapanMeOH extract partitioned between H2O and EtOAc. EtOAc extract subjected to Sephadex LH20 (CH2Cl2/MeOH, 1:1, v/v). Fraction separation on RP HPLCAcetylenic acid1H and 13C NMR, ESI-MS, UV, IR[163]
Petrosia weinbergiPorifera (Demospongiae)Acklin Island, BahamasMeOH/CHCl3 (1:1, v/v). Aqueous suspension extracted with EtOAc, EtOAc/n-BuOH (1:1), and n-BuOH. Active extracts fractionated by C18 HPLCSteroid sulfates
(Weinbersterol disulfates)
1H and 13C NMR, FAB-MS, IR[166]
Poecillastra wondoensis, Rhabdastrella wondoensis
(two-sponge association)
Porifera (Demospongiae)Cheju Island, South KoreaMeOH (70%). Extract partitioned with Et2O and H2O. Aqueous phase extracted with n-BuOH, subjected to C18 flash chromatography and Sephadex LH-20. Purification on C18 HPLCSteroidal glycosides
(Wondosterols)
1H and 13C NMR, FAB-MS, UV, IR[175]
Pseudoceratina purpureaPorifera (Demospongiae)Kaunakakai Harbor, O’ahu island, Hawaii, USAEtOH and methylene chloride. Combined extracts partitioned (hexane, methylene chloride and BuOH) Isolation: SiO2 flash column (hexane). Purification: Sephadex LH-20Bromotyramine homoserine-derived (Mololipids)1H and 13C NMR, HR-FAB-MS, UV, IR[191]
Axinyssa digitataPorifera (Demospongiae)TunisiaAcetone extract partitioned between H2O and Et2O. Aqueous residue re-extracted with n-BuOH and chromatographed on Sephadex LH-20 column (MeOH) and C18 HPLCSteroid sulfates
(Halistanol sulfates)
1H and 13C NMR, FAB-MS[165]
Siliquariaspongia sp.Porifera (Demospongiae)Motualevu reef, FijiH2O and MeOH/CH2Cl2 (1:1, v/v). n-BuOH-soluble material from the aqueous extract and CHCl3-soluble material from the organic extract chromatographed on Sephadex LH-20 (MeOH/H2O, 3:1, v/v). Purification by RP HPLCBrominated long-chain acids (Motualevic acids)1H- and 13C-NMR, LC-MS, HR-ESI-MS, FT-IR[164]
Siphonodictyon coralliphagumPorifera (Demospongiae)Lighthouse Reef and Glover Reef, BelizeEtOH. Aqueous suspension extracted with CH2Cl2, EtOAc and n-BuOH. EtOAc extract fractionated by chromatography and purified on SiO2 platesPhenolic aldehydes
(Siphonodictyal)
1H and 13C NMR, IR, UV[182]
Spheciospongia purpureaPorifera (Demospongiae)Weizhou Island, Guangxi Autonomous Region, ChinaAcetone. Extract resuspended in H2O and partitioned with Et2O. Et2O extract fractionated on SiO2 (petroleum ether/acetone, 1:0 → 0:1), Sephadex LH-20 (CH2Cl2/MeOH, 1:1). Purification by C18 HPLCLysophospholipids
(PAF(16:0), PAF (16:1 n-5), PAF (18:0), PAF (18:1 n-7), PAF (18:1 n-11), PAF (18:1 n-13))
1H and 13C NMR, IR, ESI-MS, HR-ESI-MS, LC-MS/MS[146]
Family SpongiidaePorifera (Demospongiae)Unten Port, Okinawa, JapanMeOH extract partitioned between EtOAc and H2O. H2O-soluble portions extracted with n-BuOH. EtOAc and n-BuOH, soluble materials purified by SiO2 columns and C18 HPLCSesquiterpenoid
(Sesquiterpenoid quinones, Nakijiquinones)
1H and 13C NMR, FAB-MS, UV, IR[185]
Suberites domunculaPorifera (Demospongiae)Rovinj, CroatiaMeOH and CHCl3. Combined extracts partitioned between H2O and BuOH. Organic layer fractionated by medium-pressure on C18 (linear gradient H2O → MeOH → CHCl3). Purification by RP HPLCLysophospholipids
(PAF)
1H NMR, FIA-MS, LC-MS/MS[157]
Topsentia sp.Porifera (Demospongiae)Chuuk, Federated States of MicronesiaCH2Cl2/MeOH (1:1, v/v). Extract fractionated by SPE using C18 cartridgesSteroid sulfates
(Eurysterols)
1H and 13C NMR, HR-ESI-MS, IR, UV[168]
Xestospongia sp.Porifera (Demospongiae)Rasch Pass of Madang, Papua New GuineaHexane, CH2Cl2 and EtOAc. Hexane extract subjected to flash column (gradient hexane/EtOAc (95:5, v/v) → EtOAc)Brominated FA1H and 13C NMR, IR, UV, HR-EI-MS, HR-APCI-MS, HR-FAB-MS[138]
Hyas araneus,
Podopthalmus vigil,
Lauridromia dehanni, Charybdis helleri, Portunus sanguinolentus,
Portunus pelagicus
Arthropoda (Malacostraca)Vellar Estuary, IndiaMeOHLysoglycerolipids/glycerides
FA/esters
1H and 13C NMR, ESI-MS/MS, FT-IR[148]
Meganyctiphanes norvegicaArthropoda (Malacostraca)Straits of Messina, central Mediterranean Sea, ItalyH2O/acetone (1:1, v/v). Supernatant recovered with CH₂Cl₂. Extracts fractionated by semi-preparative RP HPLC-DAD on SB-C8 columnFA
(EPA, DHA, ETA)
LC-MS, HPLC-UV-HR-MS[141]
Aplidium sp.Chordata (Ascidiacea) Northland, New ZealandMeOH-CH2Cl2 extract fractionated with RF C18 flash column (MeOH/H2O), Sephadex LH20 (MeOH), semi-preparative C18 HPLCMeroterpene derivatives
(Rossinones)
1H and 13C NMR, HR-FAB-MS, UV, IR[189]
Eunicea succineaCnidaria (Anthozoa)Mona Island, Puerto Rico,CHCl3/MeOH (1:1, v/v). Extract fractionated by SiO2 column chromatographyFA
((5Z,9Z)-14-methyl-5,9-pentadecadienoic acid)
1H and 13C NMR, GC-MS, HR-MS, IR[137]
Lobophytum crassum
Cnidaria (Anthozoa)Rameswaram, IndiaAqueous EtOH (95%), MeOH. Extract partitioned with H2O and EtOAc. EtOAc extract fractionated on SiO2 column (gradient hexane/EtOAc)Cembranoid diterpene
Ceramide
1H and 13C NMR, FAB-MS, IR[177]
Antillogorgia elisabethaeCnidaria (Anthozoa)BahamasMeOH. Extract redissolved in EtOH/H2O (2:8, v/v). EtOH/H2O extract reextracted with EtOAc, SiO2 column (hexane, 0 → 100% EtOAc/hexane, 0 → 100% MeOH/EtOAc). Fractions subjected to RP HPLC (0 → 100% H2O/Acetonitrile)Diterpenes
(Elisabethin)
1H, 13C NMR, HR-EI-MS, UV, IR[192]
Sinularia grandilobata,
Sinularia sp.
Cnidaria (Anthozoa)Andaman Islands, IndiaEtOH. Extract reextracted with EtOAc. Combined extracts fractionated on SiO2 column (gradient system hexane/EtOAc (100:0 → 0:100))Sphingolipids
Glycolipids
1H and 13C NMR, EI-MS[139]
Holothuria scabra
Echinodermata (Echinozoa)Red Sea, EgyptEtOH (70%), MeOH, EtOAc and CHCl3/MeOH (2:1, v/v)Pigments
(Carotenoids)
HPLC-UV/VIS, GC-MS[193]
Dosidicus gigasMollusca (Cephalopoda)Hermosillo, MexicoAcidified MeOH (MeOH/HCl, 99:1, v/v)Pigments
(Ommochrome)
1H and 13C NMR, FT-IR,[144]
Saccostrea glomerataMollusca
(Bivalvia)
Kovalam, Tamilnadu, IndiaHexane, EtOAc and MeOH. Purification on SiO2 column (hexane/EtOAc and EtOAc/MeOH)Sterols [Cholesta-5,22-dien-3β-ol, Cholesterol, Ergosta-5,22-dien-3-ol, (3β,22E)-],
FA (6-Octadecenoic acid, Octadecanoic acid)
GC-MS, FT-IR[171]
Table 6. Antimicrobial activity of lipids or lipid-rich extracts from marine invertebrates.
Table 6. Antimicrobial activity of lipids or lipid-rich extracts from marine invertebrates.
Scientific NameActivityTested (Micro)OrganismsAntimicrobial Testing Method/EvaluationReference Antimicrobial (Positive Control)MIC, Diameter of Inhibition Zone (IZ) or OtherRef.
Acanthodendrilla sp.
AntifungalYeast: S. cerevisiae (A364A, STX338-2C, 14028g, GT160-45C)Disk diffusion method IZ (mm): 7–11[169]
Antibacterial
Antifungal
G(+): S. aureus, B. subtilis
G(-):
E. coli,
Yeast: C. albicans
Fungi: Cladosporium herbarum
Disk diffusion method IZ (mm)
S. aureus: 7–11
B. subtilis: 7–12
E. coli: 7–12
C. albicans: 9–10
C. herbarum: 10–20
[190]
Agelas oroidesAntibacterial, AntiplasmodialAcid-fast bacterium: M. tuberculosis
Parasitic protozoa: P. falciparum,
Trypanosoma brucei rhodesiense,
T. cruzi, L. donovani
G(-): E. coli
[3H]-hypoxanthine incorporation assay, 96-well microtiter plates, inhibition of enzymatic activityArtemisinin, Benznidazole, Melarsoprol, Miltefosine, Podophyllotoxin, TriclosanIC50 (µg/mL)
Antibacterial
M. tuberculosis: 9.4–>50
E. coli: 0.07–>50
Antiprotozoal: 0.35–>30
[162]
Caminus sphaeroconia
Antibacterial
G(+): MRSA, Enterococcus (VRE)
G(-): E. coli
in vitro inhibition MIC (µg/mL)
MRSA: 12
VRE: 12
E. coli: > 100
[147]
Antibacterial
G(+): MRSA, Enterococcus (VRE)
G(-): Xanthomonas maltophilia
Plant pathogen: Pythium ultimum
Disk diffusion method MIC (µg/disk)
MRSA: 6.3–>100
VRE: 3.1–>100
X. maltophilia: 25–>100
P. ultimum: 25–>100
[176]
Dysidea arenariaAntiviralVirus: HIV-1 PFAIC50 (µM) 16.4–239.7 [184]
Dysidea sp.Antibacterial
G(+): S. aureus, B. subtilis, M. luteus
G(-): P. vulgaris, S. typhimurium, E. coli
Broth macrodilution methodLinezolidMIC (µg/mL) 0.117–>15 [183]
Erylus lendenfeldiAntifungalYeast: C. albicans MIC (µg/mL) 15.6 [172]
Erylus placentaAntifungalG(+): S. aureus
G(-): E. coli
Fungus: Mortierella ramanniana
Yeasts: S. cerevisiae (cdc28, act1-1, erg6)
Disk diffusion method IZ (mm)
M. ramanniana: 11–12
S. cerevisiae: 8–18
[174]
Euryspongia sp.AntifungalYeasts: C. albicans (ATCC 32354, wild-type) (ATCC 90873, amphotericin B-resistant)Liquid antifungal assayAmphotericin BMIC (µg/mL): 15.6–62.5 [167]
Fasciospongia sp.Antibacterial
G(+):
S. aureus (ATCC 25923, ATCC 9144), B. subtilis (ATCC 6051, ATCC 6633)
G(-):
E. coli (ATCC 11775), P. aeruginosa (ATCC 10145)
Yeast: C. albicans (ATCC 90028)
96-well microtiter platePenicillin, FluconazoleIC50 (µM)
S. aureus: 0.95–2.5
B. subtilis: 0.3–7.0
[186]
Halichondria sp.
Antibacterial AntifungalG(+): M. luteus, B. subtilis
G(-):
E. coli
Yeasts: C. neoformans,
C. albicans,
Fungi: Paecilomyces variotii, A. niger, A. fumigatus
Broth microdilution method MIC (µg/mL)
M. luteus: 0.52
C. neoformans: 0.0625
C. albicans: 2.09
P. variotii: 1.04
A. niger: 1.04
A. fumigatus: 1.04
[187]
Antibacterial AntifungalG(+): M. luteus
Yeast: C. neoformans
Fungi: T. mentagrophytes
MIC (µg/mL)
M. luteus: 4
T. mentagrophytes: 8–16
C. neoformans: 16
[188]
Haliclona simulansAnti-mycobacterial
Antitrypanosomal
Acid-fast bacterium: Mycobacterium marinum
Parasitic trypanosomatida: T. brucei
Broth microdilution methodGentamycinMIC (µM): M. marinum: 156.9–288.8
T. b. brucei: 4.58–21.56
[170]
Jaspis stelliferaAntibacterial
Antifungal
G(+): Sarcina lutea
Yeast: C. neoformans
Fungi: T. mentagrophytes
MIC (µg/mL)
S. lutea: 50
C. neoformans: 50
T. mentagrophytes: 12.5
[181]
Luffariella geometricaAntibacterialG(+): S. aureus, Micrococcus sp.
Yeast: S. cerevisiae
Disk diffusion method EC (µg/disk)
S. aureus: 100
Micrococcus sp.: 100
[178]
Luffariella variabilis
AntibacterialG(+): Streptomyces pyogenes, S. aureus Active against S. pyogenes, S. aureus[180]
AntibacterialG(+): S. aureus, B. subtilis
G(-): E. coli, P. aeruginosa
Yeast: C. albicans
Active against S. aureus, B. subtilis[179]
Melophlus sarasinorumAntibacterial
Antifungal
G(+): B. subtilis (DSM2109)
G(+): E. coli (DSM10290)
Yeast: S. cerevisiae
Disk diffusion method IZ (mm)
B. subtilis: 9
S. cerevisiae: 10–13
[173]
Oceanapia sp.Antibacterial
Antifungal
G(+):
B. subtilis, S. aureus
G(-): E. coli, P. aeruginosa
Yeast: S. cerevisiae, C. albicans (GT160-45C, cdc5, act1-1, YAT2296c)
Fungi: Penicillium chrysogenum, Mortierella ramanniana
Disk diffusion method IZ (mm)
S. cerevisiae: 6.5–10
C. albicans: 8
E. coli: 8.5–12.0
P. aeruginosa: 8.5–13.0
B. subtilis: 11.0
S. aureus: 9.5–13.5
[161]
Paragrantia cf. waguensisAntibacterialG(+):
S. aureus (IAM 12084)
G(-): E. coli (ATCC 12600)
Broth microdilution methodRifampicin, Nalidixic acidMIC (µg/mL)
S. aureus: 64
E. coli: 128
[163]
Petrosia weinbergiAntiviralViruses: Feline leukemia virus (FeLV), HIV EC50 (µg/mL)
FeLV: 4.0–5.2
HIV: 1.0
[166]
Poecillastra wondoensis, Rhabdastrella wondoensis
(two-sponge association)
Antibacterial
G(-): P. aeruginosa,
E. coli
Disk diffusion method Active concentration 10 µg/disk[175]
Pseudoceratina purpureaAntiviralVirus: HIV-1 EC50 (µM): 52.2[191]
Axinyssa digitataAntiviralViruses: HIV-1, HIV-2 EC50 (µg/mL)
HIV-1: 3–6
HIV-2: Not referred
[165]
Siliquariaspongia sp.AntibacterialG(+):
S. aureus, MRSA
Disk diffusion method, Microbroth dilution MIC50 (µg/mL)
S. aureus: 1.2–10.9
S. aureus (MRSA):
3.9–400
[164]
Siphonodictyon coralliphagumAntibacterialG(+): S. aureus,
B. subtilis
Active against S. aureus, B. subtilis[182]
Spheciospongia purpureaAntifungalYeasts: C. neoformans (32609), C. glabrata (537)
Fungi: T. rubrum (Cmccftla), A. fumigatus (07544),
Broth dilutionAmphotericin B, Fluconazole, Voriconazole, KetoconazoleMIC80 (µg/mL)
C. neoformans: 4–32
C. glabrata: 8–64
A. fumigatus: >64
T. rubrum: >64
[146]
Family SpongiidaeAntibacterial
Antifungal
G(+): B. subtilis, M. luteus, S. aureus
G(-): E. coli
Yeasts: C. albicans, C. neoformans
Fungi: A. niger
MIC (µm/mL)
B. subtilis: 33.3
E. coli: >33.3
M. luteus: 16.7–33.3
S. aureus: 33.3
C. neoformans: 8.35
C. albicans: 8.35
A. niger: 16.7
[185]
Suberites domunculaAntibacterial
Bacterium SB1 (strain isolated from S. domuncula with >98.0% similarity to the alpha-Proteobacterium (MBIC3368)Disk diffusion method IZ (mm): 4.5–6.8[157]
Topsentia sp.AntifungalG(+):MRSA,
Acid-fast bacterium: M. intracellulare
Parasitic protozoa: P. falciparum (D6 and W2 clones),
L. donovani
Yeasts: C. albicans, C. glabrata, Candida krusei, S. cerevisiae, C. neoformans
Fungus: A. fumigatus
Broth microdilution methodBeauvericinFIC (µM)
C. albicans: 0.2–1.8
S. cerevisiae: 0.08–1.34
[168]
Xestospongia sp.AntibacterialG(+): MRSA, S. mutans, S. sobrinusDisk diffusion method IZ (mm)
MRSA: 12
S. mutans: 17
S. sobrinus: 14
[138]
Hyas araneus, Podopthalmus vigil, Lauridromia dehanni, Charybdis helleri, Portunus sanguinolentus, Portunus pelagicusAntibacterial
Antifungal
G(+): S. aureus, MRSA, S. pyogenes
G(-): E. coli, P. aeruginosa, S. typhi, S. flexneri, Klebsiella sp., V. cholerae, Acinetobacter sp.
Yeasts: Rhodotorula
sp., C. albicans, C. neoformans
Fungi: A. fumigatus, A. niger
Disk diffusion methodPenicillin, KetoconazoleIZ (mm)
S. pyogenes: 1
S. typhi: 1–3
S. flexneri: 1–6
V. cholerae: 1–4
Acinetobacter sp.: 1
[148]
Meganyctiphanes norvegicaAntibacterialG(+): MRSA, MB5393, MSSA, ATCC 29213
G(-): E. coli (ATCC 25922), K. pneumoniae (ATCC 700603)
Acid-fast bacterium: M. tuberculosis (H37Ra ATCC 25177)
Well plate, REMA methodVancomycin hydrochloride, Aztreonam, Gentamycin sulfateMIC (µg/mL)
MRSA: 80–320
MSSA: 320
M. tuberculosis: 320
[141]
Aplidium sp.Antibacterial
Antiviral
Antifungal
G(+): B. subtilis
Fungi: T. mentagrophytes
Virus: HSV-1
Disk diffusion method IZ (mm)
B. subtilis/T. mentagrophytes: 3–6
Antiviral activity at 2 μg/disk
[189]
Eunicea succineaAntibacterialG(+): S. aureus (ATCC 25923), E. faecalis (ATCC 29212)
G(-): P. aeruginosa (ATCC 27853), E. coli (ATCC 25922)
Broth microdilution method MIC (µmol/mL)/IC50 (µg/mL)
S. aureus: 0.24/36
E. faecalis: 0.16/<10
[137]
Lobophytum crassum
AntibacterialG(+): S. epidermidis, B. subtilis, S. aureus
G(-): P. aeruginosa
Disk diffusion methodAmpicillinIZ (mm)
S. epidermidis: 9.5–16.5
B. subtilis: 8.5–18.0
S. aureus: 9.0–19.5
P. aeruginosa: 9.0–14.0
[177]
Antillogorgia elisabethaeAntibacterial
G(+): S. pyogenes (ATCC 19615), S. aureus (ATCC 25923), E. faecalis (ATCC 19433)
G(-): E. coli (ATCC 25933), P. aeruginosa (ATCC 27853)
Disk diffusion method MIC (µg/mL)/IZ (mm)
S. pyogenes: 0.8–1.0/12–17
S. aureus: 2.0–2.3/8–11
E. faecalis: 3.2–3.8/8–9
[192]
Sinularia grandilobata,
Sinularia sp.
Antibacterial
Antifungal
G(+): B. subtilis (MTCC 441), Bacillus pumilus (NCIM 2327)
G(-): E. coli
(MTCC 443), P. aeruginosa (MTCC 1688)
Yeast: C. albicans (MTCC 183)
Fungi: A. niger (MTCC 1344), Rhizopus oryzae (MTCC 1987)
Disk diffusion method IZ (mm)
B. subtilis: 11–18
B. pumilus: 11–16
E. coli: 11–17
P. aeruginosa: 11–17
C. albicans: 8–17
A. niger: 10–16
R. oryzae: 10–15
[139]
Holothuria scabra
Antibacterial
G(+): S. aureus (ATCC 6538), E. faecalis
G(-): P. aeruginosa (ATCC 8739), V. damsela, E. coli
Well-cut diffusion technique AU
S. aureus: 1.2–2.8
E. faecalis: 1.7–3.2
P. aeruginosa: 1.4–1.8
V. damsela: 1.6
E. coli: 1.2
[193]
Dosidicus gigasAntibacterial
Antifungal
G(+): B. cereus (CCM 2010), Clostridium perfringens (CCM 4991), Listeria monocytogenes (CCM 4699), S. aureus subs. aureus (CCM 2461)
G(-): Haemophilus influenza (CCM 4456), K. pneumoniae (CCM 2318), S. enterica subs. enterica (CCM 3807)
Yeasts: C. albicans (CCM 8186), C. glabrata (CCM 8270), C. tropicalis (CCM 8223)
Fungi: Aspergillus clavatus, A. flavus, Aspergillus versicolor, Penicillium chrisogenum, Penicillium griseofulvum, Penicillium expansum
Disk diffusion method Inhibition (%)
B. cereus: 39.4
C. perfringens: 45.5
L. monocytogenes: 60.7
S. aureus subs. aureus: 57.8
H. influenza: 54.5
K. pneumoniae: 39.4
S. enterica subs. enterica: 93.9
C. albicans: 66.7
C. glabrata: 42.4
C. tropicalis: 33.3
A. clavatus: 48.4
A. flavus: 42.4
A. versicolor: 42.4
P. chrisogenum: 39.4
P. griseofulvum: 42.4
P. expansum: 48.5
[144]
Saccostrea glomerataAntibacterial
Antifungal
G(+): S. aureus
G(-): P. aeruginosa, V. harveyi, A. hydrophila, P. aeruginosa, V. harveyi, V. parahaemolyticus
Yeast: C. albicans
Fungi: A. niger, A. flavus, Fusarium sp.
Virus: White spot syndrome virus (WSSV)
Disk diffusion method
IZ (mm)
P. aeruginosa: 4.1–16.0
V. harveyi: 3.8–14.9
A. hydrophila: 5.1–14.5
A. niger: No activity–High activity
C. albicans: No activity–High activity
Fusarium sp: No activity–High activity
Antiviral activity: PI < 91.85%
[171]
Abbreviations: AU: activity unit for the clear zone; EC: effective concentration; FIC: fractional inhibitory concentration; IZ: inhibition zone; MIC: minimum inhibitory concentration; PI: percentage inhibition.

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MDPI and ACS Style

Alves, E.; Dias, M.; Lopes, D.; Almeida, A.; Domingues, M.d.R.; Rey, F. Antimicrobial Lipids from Plants and Marine Organisms: An Overview of the Current State-of-the-Art and Future Prospects. Antibiotics 2020, 9, 441. https://doi.org/10.3390/antibiotics9080441

AMA Style

Alves E, Dias M, Lopes D, Almeida A, Domingues MdR, Rey F. Antimicrobial Lipids from Plants and Marine Organisms: An Overview of the Current State-of-the-Art and Future Prospects. Antibiotics. 2020; 9(8):441. https://doi.org/10.3390/antibiotics9080441

Chicago/Turabian Style

Alves, Eliana, Marina Dias, Diana Lopes, Adelaide Almeida, Maria do Rosário Domingues, and Felisa Rey. 2020. "Antimicrobial Lipids from Plants and Marine Organisms: An Overview of the Current State-of-the-Art and Future Prospects" Antibiotics 9, no. 8: 441. https://doi.org/10.3390/antibiotics9080441

APA Style

Alves, E., Dias, M., Lopes, D., Almeida, A., Domingues, M. d. R., & Rey, F. (2020). Antimicrobial Lipids from Plants and Marine Organisms: An Overview of the Current State-of-the-Art and Future Prospects. Antibiotics, 9(8), 441. https://doi.org/10.3390/antibiotics9080441

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