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Special Issue "Antimicrobial Plant Extracts and Phytochemicals"

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A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Plant-Derived Antibiotics".

Deadline for manuscript submissions: closed (31 January 2020).

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Special Issue Editors

Prof. Dr. Marcello Iriti
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Department of Agricultural and Environmental Sciences, Milan State University, Milan, Italy
Interests: environmental pollution; agrochemicals; mycotoxins; biomonitoring
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Elena Maria Varoni
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Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy
Interests: oral diseases; oral health; bioactive phytochemicals; biomaterials; nanomaterials; drug delivery systems
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Prof. Dr. Sara Vitalini
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Department of Agricultural and Environmental Sciences, Università degli Studi di Milano, Milan, Italy
Interests: crop protection; plant diseases; bioactivity; phytochemistry; ethnopharmacology; natural products
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Special Issue Information

Dear Colleagues,

The urgent need for novel antimicrobial drugs to reduce the global burden of infectious diseases has greatly stimulated the exploration of plant products as a source of novel and effective phytotherapeutic agents. Indeed, plant products represent a nearly unlimited source of (multitarget) active ingredients, consisting in complex mixtures of hundreds of different compounds that may be synergistically active once administered. In addition, plant extracts and phytochemicals can be useful in adjuvant therapy to improve the efficacy of conventional antimicrobials, to decrease their adverse effects, and to reverse multidrug resistance, the latter an emerging and very critical topic due to the genetic plasticity and environmental adaptability of pathogenic microorganisms. Not least, selected phytochemicals can also be used as a template for the development of new scaffolds of drugs.

Prof. Dr. Marcello Iriti
Dr. Elena Maria Varoni
Dr. Sara Vitalini
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

plant products
marine plant products
antibiotics
fungicides
antibacterial agents
antifungal/antimycotic agents
crop protection
pesticides
antibiotic resistance
multi-drug resistance
cross-resistance
ethnopharmacology
preclinical (in vitro/in vivo) studies
clinical/in human studies
evidence-based medicine
systematic reviews & meta-analyses

Published Papers (10 papers)

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Editorial

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Open AccessEditorial

Humans, Animals, Food and Environment: One Health Approach against Global Antimicrobial Resistance

Marcello Iriti

Sara Vitalini

and

Elena Maria Varoni

Antibiotics 2020, 9(6), 346; https://doi.org/10.3390/antibiotics9060346 - 19 Jun 2020

Cited by 2 | Viewed by 1313

Abstract

Antimicrobial resistance represents one of the most relevant threats to global public health and food security, affecting anyone, of any age, in any country and is responsible for longer hospital stays, higher medical costs and increased mortality. Resistant microorganisms are present in humans, animals, food and the environment, and, therefore, the One Health approach is very promising to counteract antimicrobial resistance, since human health and animal health are connected to each other and with the environment and the latter a potential source of resistant microorganisms. In this context, the need for novel antimicrobial drugs has stimulated the exploration of plant products as a source of novel phytotherapeutics able to reverse antimicrobial resistance when used in combination with conventional antibiotic drugs. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals)

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Research

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Open AccessArticle

Abundant Extractable Metabolites from Temperate Tree Barks: The Specific Antimicrobial Activity of Prunus Avium Extracts

and

Antibiotics 2020, 9(3), 111; https://doi.org/10.3390/antibiotics9030111 - 04 Mar 2020

Cited by 6 | Viewed by 2075

Abstract

Tree barks are mainly considered as wood wastes from forestry activities, but represent valuable resources as they may contain antimicrobial compounds. Here, we aimed to evaluate the possible antimicrobial activities of bark extracts and to characterize the chemical composition of the most active extract. Ten methanol bark extracts were tested in vitro against 17 bacterial strains and 5 yeast strains, through minimum inhibitory concentration (MIC) and minimum bactericidal (or fungicidal) concentration (MBC/MFC) assays. The extract from Prunus avium (E2-4) displayed the largest bactericidal activity against Gram-positive bacteria, with a lethal effect on 6 out of 8 strains. Antibiofilm assays of E2-4 were performed by crystal violet staining and enumeration of adhered bacteria. Assays demonstrated a biofilm inhibitory effect of E2-4 against Staphylococcus aureus CIP 53.154 at concentrations equal to or higher than 250 µg/mL. Chemical profiling of E2-4 by ¹³C nuclear magnetic resonance (NMR) revealed the presence of dihydrowogonin as a major constituent of the extract. E2-4 was fractionated by centrifugal partition chromatography and the three fractions containing dihydrowogonin were tested for their antibacterial and antibiofilm activities, revealing similar activities to those of E2-4. Dihydrowogonin was positively assessed as an interesting antimicrobial compound, which could be valued from wastes of Prunus avium barks. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals)

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Open AccessArticle

In vitro Antibiotic and Modulatory Activity of Mesosphaerum suaveolens (L.) Kuntze against Candida strains

Adrielle Rodrigues Costa

José Weverton Almeida Bezerra

Rafael Pereira da Cruz

Maria Audilene de Freitas

Viviane Bezerra da Silva

João Cruz Neto

Antonia Thassya Lucas dos Santos

Maria Flaviana Bezerra Morais Braga

Leomara Andrade da Silva

Antonia Eliene Duarte

and

Luiz Marivando Barros

Antibiotics 2020, 9(2), 46; https://doi.org/10.3390/antibiotics9020046 - 27 Jan 2020

Cited by 8 | Viewed by 1631

Abstract

The emergence of fungal resistance to commercial drugs has been a major problem for the WHO. In this context, research with natural products is promising in the discovery of new active substances. Thus, this work evaluated the antifungal effect of a medicinal plant (i.e., Mesosphaerum suaveolens) against strains of the genus Candida, tested the combined effect with the drug fluconazole, and, finally, determined the phenolic constituents present in the species. Initially, aqueous extracts of leaves (AELMs) and aerial parts (AEAPMs) of the species were prepared. For microbiological assays, the minimum fungicidal concentration was determined by broth microdilution, and the combined effect of fluconazole extracts were verified by sub-inhibitory microdilution concentrations (CFM/8) followed by spectrophotometric readings which were used to determine the IC₅₀. HPLC detected the presence of flavonoids and phenolic acids, detecting eight compounds present in the samples of which caffeic acid and quercetin were major components. The AELMs modulated fluconazole activity since it decreased fluconazole’s IC₅₀ from 7.8 µg/mL to an IC₅₀ of 4.7 µg/mL (CA LM 77) and from 28.8 µg/mL to 18.26 µg/mL (CA INCQS 40006) for the C. albicans strains. The AEAPMs were able to potentiate the effect of fluconazole more effectively than the AELMs. Such an effect was significant for the 16 µg/mL concentration for CA LM 77 and 32 µg/mL for CA INCQS 40006. The AEAPMs as well as the AELMs presented clinically relevant activities for C. tropicalis strains. For the C. tropicalis LM 23 strain, the AEPMs obtained an IC₅₀ of 25 µg/mL and the AELMs an IC₅₀ of 359.9 µg/mL. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals)

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Open AccessArticle

Effect of α-Bisabolol and Its β-Cyclodextrin Complex as TetK and NorA Efflux Pump Inhibitors in Staphylococcus aureus Strains

Rafael Pereira da Cruz

Thiago Sampaio de Freitas

Maria do Socorro Costa

Antonia Thassya Lucas dos Santos

Fábia Ferreira Campina

Raimundo Luiz Silva Pereira

José Weverton Almeida Bezerra

Lucindo José Quintans-Júnior

Adriano Antunes De Souza Araújo

José Pinto De Siqueira Júnior

Marcello Iriti

Elena Maria Varoni

Irwin Rose Alencar De Menezes

Henrique Douglas Melo Coutinho

and

Maria Flaviana Bezerra Morais-Braga

Antibiotics 2020, 9(1), 28; https://doi.org/10.3390/antibiotics9010028 - 14 Jan 2020

Cited by 10 | Viewed by 2047

Abstract

Efflux pumps are proteins present in the plasma membrane of bacteria, which transport antibiotics and other compounds into the extracellular medium, conferring resistance. The discovery of natural efflux pump inhibitors is a promising alternative. α-Bisabolol is a sesquiterpene isolated from several plants such as Matricaria chamomilla L. and has important properties such as antibacterial and anti-inflammatory activity. Currently, the formation of inclusion complexes with β-Cyclodextrin has been used for improving the physicochemical characteristics of the host molecule. This study evaluated the effect of α-Bisabolol, in isolation and in complexation with β-Cyclodextrin, as TetK and NorA efflux pump inhibitors in Staphylococcus aureus strains. The minimum inhibitory concentration (MIC) was determined. Subsequently, inhibitory activity over the pumps was observed by an MIC reduction for the antibiotics, by using subinhibitory concentrations (MIC/8) in combination with tetracycline and norfloxacin. The MIC of the compounds was ≥1024 μg/mL. α-Bisabolol potentiated the action of tetracycline and reduced the MIC of norfloxacin to a clinically relevant concentration. The complexed substance showed synergism however, the effect of the isolated α-Bisabolol was superior to the complex. These results indicate α-Bisabolol is a potential substance to be used as an efflux pump inhibitor. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals)

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Open AccessArticle

Essential Oil of Croton ceanothifolius Baill. Potentiates the Effect of Antibiotics against Multiresistant Bacteria

Ana C. J. de Araújo

Priscilla R. Freitas

Cristina Rodrigues dos Santos Barbosa

Débora F. Muniz

Janaína Esmeraldo Rocha

José B. de Araújo Neto

Maria M. C. da Silva

Talysson F. Moura

Raimundo L. S. Pereira

and

Henrique D. Melo Coutinho

Antibiotics 2020, 9(1), 27; https://doi.org/10.3390/antibiotics9010027 - 14 Jan 2020

Cited by 4 | Viewed by 1812

Abstract

This study is a pioneer in reporting the antibacterial properties of the species Croton ceanothifolius Baill. The genus Croton belongs to the family Euphorbiaceae composed of numerous species with documented biological activities. However, the pharmacological properties of C. ceanothifolius remain poorly understood. The leaves of this plant were submitted to hydrodistillation for essential oil (CcEO) extraction and the phytochemical characterization of the oil was performed by GC/MS. The minimum inhibitory concentration of the CcEO was determined for the evaluation of antibacterial activity against multiresistant strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. The antibiotic-modulating activity of the oil, in combination with antibiotics, was also evaluated. The combination of the CcEO with penicillin, norfloxacin, and gentamicin presented a synergistic effect. This effect was more significant for the association with antibiotics of the quinolone and aminoglycoside classes against Escherichia coli. The association of oil with gentamicin showed better results with regard to the Gram-positive strain. The association of the oil with norfloxacin against P. aeruginosa also showed synergism, but the association with penicillin did not change the effect of this antibiotic. Thus, it is concluded that C. ceanothifolius essential oil selectively potentiates the action of antibiotics against multiresistant strains. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals)

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Open AccessArticle

Photoinduced Antibacterial Activity of the Essential Oils from Eugenia brasiliensis Lam and Piper mosenii C. DC. by Blue Led Light

Antibiotics 2019, 8(4), 242; https://doi.org/10.3390/antibiotics8040242 - 28 Nov 2019

Cited by 5 | Viewed by 1797

Abstract

The objective of this work was to evaluate the phytochemical composition and the antibacterial and antibiotic-modulating activities of the essential oils of Eugenia brasiliensis Lam (OEEb) and Piper mosenii C. DC (OEPm) singly or in association with blue LED (Light-emitting diode) light. The antibacterial and antibiotic-modulatory activities of the essential oils on the activity of aminoglycosides were evaluated to determine the minimum inhibitory concentration (MIC, μg/mL) in the presence or absence of exposure to blue LED light. The chemical analysis showed α-pinene and bicyclogermacrene as major constituents of OEPm, whereas α-muurolol was the main compound of OEEb. Both OEEb and OEPm showed MIC ≥ 512 μg/mL against the strains under study. However, the association of these oils with the blue LED light enhanced the action of the aminoglycosides amikacin and gentamicin. In conclusion, the association of aminoglycosides with the blue LED light and essential oils was effective against resistant bacteria. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals)

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Open AccessArticle

UPLC-MS-ESI-QTOF Analysis and Antifungal Activity of the Spondias tuberosa Arruda Leaf and Root Hydroalcoholic Extracts

Antonia Thassya Lucas dos Santos

Joara Nályda Pereira Carneiro

Rafael Pereira da Cruz

Débora Lima Sales

Jacqueline Cosmo Andrade

Waltécio de Oliveira Almeida

José Galberto Martins da Costa

Paulo Riceli Vasconcelos Ribeiro

Edy Sousa de Brito

Francisco Lucas Alves Batista

Francisco Ernani Alves Magalhães

Marcello Iriti

Maria Flaviana Bezerra Morais-Braga

and

Henrique Douglas Melo Coutinho

Antibiotics 2019, 8(4), 240; https://doi.org/10.3390/antibiotics8040240 - 28 Nov 2019

Cited by 4 | Viewed by 2031

Abstract

The aim of this study was to identify and evaluate the chemical compositions and effects of the S. tuberosa leaf and root hydroalcoholic extracts (HELST and HERST) against different strains of Candida. Chemical analysis was performed by Ultra-Performance Liquid Chromatography Coupled to Quadrupole/Time of Flight System (UPLC-MS-ESI-QTOF). The Inhibitory Concentration of 50% of the growth (IC₅₀₎ as well as the intrinsic and combined action of the extracts with the antifungal fluconazole (FCZ) were determined by the microdilution method while the minimum fungicidal concentrations (MFCs) and the effect on fungal morphological transitions were analyzed by subculture and in humid chambers, respectively. From the preliminary phytochemical analysis, the phenols and flavonoids were the most abundant. The intrinsic IC₅₀ values for HELST ranged from 5716.3 to 7805.8 µg/mL and from 6175.4 to 51070.9 µg/mL for the HERST, whereas the combination of the extracts with fluconazole presented IC₅₀ values from 2.65 to 278.41 µg/mL. The MFC of the extracts, individually, for all the tested strains was ≥16384 µg/mL. When fluconazole was combined with each extract, the MFC against CA URM 5974 was reduced (HELST: 2048 and HERST: 4096 µg/mL). Synergism was observed against standard C. albicans (CA) and C. tropicalis (CT) strains and with the root extract against the CT isolate. The leaf extract inhibited the morphological transition of all strains while the root extract inhibited only CT strains. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals)

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Open AccessArticle

In Vitro Antibacterial Activity and Mechanism of Vanillic Acid against Carbapenem-Resistant Enterobacter cloacae

and

Antibiotics 2019, 8(4), 220; https://doi.org/10.3390/antibiotics8040220 - 13 Nov 2019

Cited by 13 | Viewed by 2259 | Retraction

Abstract

Vanillic acid (VA) is a flavoring agent found in edible plants and fruits. Few recent studies exhibited robust antibacterial activity of VA against several pathogen microorganisms. However, little was reported about the effect of VA on carbapenem-resistant Enterobacter cloacae (CREC). The purpose of the current study was to assess in vitro antimicrobial and antibiofilm activities of VA against CREC. Here, minimum inhibitory concentrations (MIC) of VA against CREC was determined via gradient diffusion method. Furthermore, the antibacterial mode of VA against CREC was elucidated by measuring changes in intracellular adenosine triphosphate (ATP) concentration, intracellular pH (pH_in), cell membrane potential and membrane integrity. In addition, antibiofilm formation of VA was measured by crystal violet assay and visualized with field emission scanning electron microscopy (FESEM) and confocal laser scanning microscopy (CLSM). The results showed that MIC of VA against E. cloacae was 600 μg/mL. VA was capable of inhibiting the growth of CREC and destroying the cell membrane integrity of CREC, as confirmed by the decrease of intracellular ATP concentration, pH_in and membrane potential as well as distinctive variation in cellular morphology. Moreover, crystal violet staining, FESEM and CLSM results indicated that VA displayed robust inhibitory effects on biofilm formation of CREC and inactivated biofilm-related CREC cells. These findings revealed that VA exhibits potent antibacterial activity against CREC, and thus has potential to be exploited as a natural preservative to control the CREC associated infections. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals)

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Open AccessArticle

Decoding Antioxidant and Antibacterial Potentials of Malaysian Green Seaweeds: Caulerpa racemosa and Caulerpa lentillifera

and

Antibiotics 2019, 8(3), 152; https://doi.org/10.3390/antibiotics8030152 - 17 Sep 2019

Cited by 24 | Viewed by 3467

Abstract

Seaweeds are gaining a considerable amount of attention for their antioxidant and antibacterial properties. Caulerpa racemosa and Caulerpa lentillifera, also known as ‘sea grapes’, are green seaweeds commonly found in different parts of the world, but the antioxidant and antibacterial potentials of Malaysian C. racemosa and C. lentillifera have not been thoroughly explored. In this study, crude extracts of the seaweeds were prepared using chloroform, methanol, and water. Total phenolic content (TPC) and total flavonoid content (TFC) were measured, followed by in vitro antioxidant activity determination using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Antibacterial activities of these extracts were tested against Methicillin-resistant Staphylococcus aureus (MRSA) and neuropathogenic Escherichia coli K1. Liquid chromatography–mass spectrometry (LCMS) analysis was then used to determine the possible compounds present in the extract with the most potent antioxidant and antibacterial activity. Results showed that C. racemosa chloroform extract had the highest TPC (13.41 ± 0.86 mg GAE/g), antioxidant effect (EC₅₀ at 0.65 ± 0.03 mg/mL), and the strongest antibacterial effect (97.7 ± 0.30%) against MRSA. LCMS analysis proposed that the chloroform extracts of C. racemosa are mainly polyunsaturated and monounsaturated fatty acids, terpenes, and alkaloids. In conclusion, C. racemosa can be a great source of novel antioxidant and antibacterial agents, but isolation and purification of the bioactive compounds are needed to study their mechanism of action. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals)

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Review

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Open AccessReview

Anti-Fungal Efficacy and Mechanisms of Flavonoids

Mohammed Saleh Al Aboody

and

Suresh Mickymaray

Antibiotics 2020, 9(2), 45; https://doi.org/10.3390/antibiotics9020045 - 26 Jan 2020

Cited by 48 | Viewed by 3993

Abstract

The prevalence of fungal infections is growing at an alarming pace and the pathogenesis is still not clearly understood. Recurrence of these fungal diseases is often due to their evolutionary avoidance of antifungal resistance. The development of suitable novel antimicrobial agents for fungal diseases continues to be a major problem in the current clinical field. Hence, it is urgently necessary to develop surrogate agents that are more effective than conventional available drugs. Among the remarkable innovations from earlier investigations on natural-drugs, flavonoids are a group of plant-derived substances capable of promoting many valuable effects on humans. The identification of flavonoids with possible antifungal effects at small concentrations or in synergistic combinations could help to overcome this problem. A combination of flavonoids with available drugs is an excellent approach to reduce the side effects and toxicity. This review focuses on various naturally occurring flavonoids and their antifungal activities, modes of action, and synergetic use in combination with conventional drugs. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals)

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