Microbial Natural Products as a Source of Novel Antimicrobials

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Novel Antimicrobial Agents".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 17365

Special Issue Editors


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Guest Editor
1. Faculty of Engineering, Lusofona University, Campo Grande, 376 1749-024 Lisboa, Portugal
2. Linking Landscape Environment Agriculture and Food Research Center (LEAF), Associated Laboratory TERRA, Instituto Superior de Agronomia, Universidade de Lisboa, Tapada da Ajuda, 1349-017 Lisboa, Portugal
Interests: biopreservatives; bioactive compounds; antimicrobial peptides; foodborne pathogens; food microbiology and safety; wine microbial control; molecular biology

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Guest Editor
CBIOS – Research Center for Biosciences and Health Technologies, Universidade Lusófona, 1749-024 Lisbon, Portugal
Interests: formulation of cosmetics; health products and nutraceutics; antimicribial natural products; study of new cosmetic preservatives; valorization and reclassification of wastes and food by-products for use in pharmaceutical and food industry; microbiology and quality control; toxicology evaluation and efficacy of the dermatological cosmetics

E-Mail Website
Guest Editor
Linking Landscape Environment Agriculture and Food Research Center (LEAF), Associated Laboratory TERRA, Instituto Superior de Agronomia, Universidade de Lisboa, Tapada da Ajuda, 1349-017 Lisboa, Portugal
Interests: foodborne pathogens; virulence; microbial susceptibility to biocides; microbial active compounds; food microbiology and safety

Special Issue Information

Dear Colleagues,

Microbial natural products are molecules of significant interest in the development of novel antimicrobial agents.

Over the last decades, there have been reports of some microbial secondary metabolites, such as antimicrobial peptides, bacteriocins, and mycocins, with potential application in the food, agriculture, and pharmaceutical industries. However, few of them have been implemented as viable alternatives to the traditional antimicrobial agents, e.g., nisin and natamycin in food products.

Is crucial to fulfil the growing demand for more natural and eco-friendly biocides/preservatives applied in food products, crops, and cosmetics and to successfully achieve advancements in the development and implementation of novel less toxic, broad-spectrum antimicrobial agents.

Therefore, this Special Issue of Antibiotics seeks reviews, research papers, and short communications that can improve on the existing knowledge about microbial natural products with the potential to be an effective and less toxic alternative to the usual antibiotics, biocides, or chemical preservatives used nowadays. Thus, research related to the discovery of antimicrobial peptides, bacteriocins, and mycocins and their mode of action and application in food safety, food microbial control, agriculture, cosmetics, and human and animal health are welcomed.

Dr. Patricia Branco
Dr. Marc Maresca
Dr. Elisabete Muchagato Mauricio
Dr. Luisa Brito
Guest Editors

Manuscript Submission Information

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Keywords

  • antimicrobial peptides
  • mycocins
  • bacteriocins
  • antimicrobial activity
  • biopreservatives

Published Papers (8 papers)

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Research

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24 pages, 8560 KiB  
Article
Hybrid Caffeic Acid-Based DHFR Inhibitors as Novel Antimicrobial and Anticancer Agents
by Renu Sehrawat, Ritu Pasrija, Priyanka Rathee, Deepika Kumari, Anurag Khatkar, Esra Küpeli Akkol and Eduardo Sobarzo-Sánchez
Antibiotics 2024, 13(6), 479; https://doi.org/10.3390/antibiotics13060479 - 23 May 2024
Viewed by 648
Abstract
A novel series of 1,2,4-triazole analogues of caffeic acid was designed, synthesized, characterized, and assessed for their capacity to inhibit DHFR, as well as their anticancer and antimicrobial properties. A molecular docking analysis was conducted on DHFR, utilizing PDB IDs 1U72 and 2W9S, [...] Read more.
A novel series of 1,2,4-triazole analogues of caffeic acid was designed, synthesized, characterized, and assessed for their capacity to inhibit DHFR, as well as their anticancer and antimicrobial properties. A molecular docking analysis was conducted on DHFR, utilizing PDB IDs 1U72 and 2W9S, aiming to design anticancer and antimicrobial drugs, respectively. Among all the synthesized derivatives, compound CTh7 demonstrated the highest potency as a DHFR inhibitor, with an IC50 value of 0.15 μM. Additionally, it exhibited significant cytotoxic properties, with an IC50 value of 8.53 µM. The molecular docking analysis of the CTh7 compound revealed that it forms strong interactions with key residues of homo sapiens DHFR such as Glu30, Phe34, Tyr121, Ile16, Val115, and Phe31 within the target protein binding site and displayed excellent docking scores and binding energy (−9.9; −70.38 kcal/mol). Additionally, synthesized compounds were screened for antimicrobial properties, revealing significant antimicrobial potential against bacterial strains and moderate effects against fungal strains. Specifically, compound CTh3 exhibited notable antibacterial efficacy against Staphylococcus aureus (MIC = 5 µM). Similarly, compound CTh4 demonstrated significant antibacterial activity against both Escherichia coli and Pseudomonas aeruginosa, with MIC values of 5 µM for each. A docking analysis of the most active antimicrobial compound CTh3 revealed that it forms hydrogen bonds with Thr121 and Asn18, a π–cation bond with Phe92, and a salt bridge with the polar residue Asp27. Full article
(This article belongs to the Special Issue Microbial Natural Products as a Source of Novel Antimicrobials)
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17 pages, 4413 KiB  
Article
Enhancing Bioactive Compound Classification through the Synergy of Fourier-Transform Infrared Spectroscopy and Advanced Machine Learning Methods
by Pedro N. Sampaio and Cecília C. R. Calado
Antibiotics 2024, 13(5), 428; https://doi.org/10.3390/antibiotics13050428 - 9 May 2024
Viewed by 815
Abstract
Bacterial infections and resistance to antibiotic drugs represent the highest challenges to public health. The search for new and promising compounds with anti-bacterial activity is a very urgent matter. To promote the development of platforms enabling the discovery of compounds with anti-bacterial activity, [...] Read more.
Bacterial infections and resistance to antibiotic drugs represent the highest challenges to public health. The search for new and promising compounds with anti-bacterial activity is a very urgent matter. To promote the development of platforms enabling the discovery of compounds with anti-bacterial activity, Fourier-Transform Mid-Infrared (FT-MIR) spectroscopy coupled with machine learning algorithms was used to predict the impact of compounds extracted from Cynara cardunculus against Escherichia coli. According to the plant tissues (seeds, dry and fresh leaves, and flowers) and the solvents used (ethanol, methanol, acetone, ethyl acetate, and water), compounds with different compositions concerning the phenol content and antioxidant and antimicrobial activities were obtained. A principal component analysis of the spectra allowed us to discriminate compounds that inhibited E. coli growth according to the conventional assay. The supervised classification models enabled the prediction of the compounds’ impact on E. coli growth, showing the following values for accuracy: 94% for partial least squares-discriminant analysis; 89% for support vector machine; 72% for k-nearest neighbors; and 100% for a backpropagation network. According to the results, the integration of FT-MIR spectroscopy with machine learning presents a high potential to promote the discovery of new compounds with antibacterial activity, thereby streamlining the drug exploratory process. Full article
(This article belongs to the Special Issue Microbial Natural Products as a Source of Novel Antimicrobials)
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17 pages, 9108 KiB  
Article
Untargeted MS-Based Metabolomic Analysis of Termite Gut-Associated Streptomycetes with Antifungal Activity against Pyrrhoderma noxium
by Cherrihan Adra, Trong D. Tran, Keith Foster, Russell Tomlin and D. İpek Kurtböke
Antibiotics 2023, 12(9), 1373; https://doi.org/10.3390/antibiotics12091373 - 28 Aug 2023
Cited by 2 | Viewed by 1529
Abstract
Pyrrhoderma noxium is a plant fungal pathogen that induces the disease of brown root rot in a large variety of tree species. It is currently infecting many of the amenity trees within Brisbane City of Queensland, Australia. Steering away from harmful chemical fungicides, [...] Read more.
Pyrrhoderma noxium is a plant fungal pathogen that induces the disease of brown root rot in a large variety of tree species. It is currently infecting many of the amenity trees within Brisbane City of Queensland, Australia. Steering away from harmful chemical fungicides, biological control agents offer environmentally friendly alternatives. Streptomycetes are known for their production of novel bioactive secondary metabolites with biocontrol potential, particularly, streptomycete symbionts isolated from unique ecological niches. In this study, 37 termite gut-associated actinomycete isolates were identified using molecular methods and screened against P. noxium. A majority of the isolates belonged to the genus Streptomyces, and 15 isolates exhibited strong antifungal activity with up to 98.5% mycelial inhibition of the fungal pathogen. MS/MS molecular networking analysis of the isolates’ fermentation extracts revealed several chemical classes with polyketides being among the most abundant. Most of the metabolites, however, did not have matches to the GNPS database, indicating potential novel antifungal compounds in the active extracts obtained from the isolates. Pathway enrichment and overrepresentation analyses revealed pathways relating to polyketide antibiotic production, among other antibiotic pathways, further confirming the biosynthetic potential of the termite gut-associated streptomycetes with biocontrol potential against P. noxium. Full article
(This article belongs to the Special Issue Microbial Natural Products as a Source of Novel Antimicrobials)
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17 pages, 1639 KiB  
Article
Exploring the Multifaceted Potential of a Peptide Fraction Derived from Saccharomyces cerevisiae Metabolism: Antimicrobial, Antioxidant, Antidiabetic, and Anti-Inflammatory Properties
by Patrícia Branco, Elisabete Muchagato Maurício, Ana Costa, Diogo Ventura, Catarina Roma-Rodrigues, Maria Paula Duarte, Alexandra R. Fernandes and Catarina Prista
Antibiotics 2023, 12(8), 1332; https://doi.org/10.3390/antibiotics12081332 - 18 Aug 2023
Cited by 3 | Viewed by 1764
Abstract
The rising demand for minimally processed, natural, and healthier food products has led to the search for alternative and multifunctional bioactive food components. Therefore, the present study focuses on the functional proprieties of a peptide fraction derived from Saccharomyces cerevisiae metabolism. The antimicrobial [...] Read more.
The rising demand for minimally processed, natural, and healthier food products has led to the search for alternative and multifunctional bioactive food components. Therefore, the present study focuses on the functional proprieties of a peptide fraction derived from Saccharomyces cerevisiae metabolism. The antimicrobial activity of the peptide fraction is evaluated against various foodborne pathogens, including Candida albicans, Candida krusei, Escherichia coli, Listeria monocytogenes, and Salmonella sp. The peptide fraction antioxidant properties are assessed using FRAP and DPPH scavenging capacity assays. Furthermore, the peptide fraction’s cytotoxicity is evaluated in colorectal carcinoma and normal colon epithelial cells while its potential as an antidiabetic agent is investigated through α-amylase and α-glucosidase inhibitory assays. The results demonstrate that the 2–10 kDa peptide fraction exhibits antimicrobial effects against all tested microorganisms, except C. krusei. The minimal inhibitory concentration for E. coli, L. monocytogenes, and Salmonella sp. remains consistently low, at 0.25 mg/mL, while C. albicans requires a higher concentration of 1.0 mg/mL. Furthermore, the peptide fraction displays antioxidant activity, as evidenced by DPPH radical scavenging activity of 81.03%, and FRAP values of 1042.50 ± 32.5 µM TE/mL at 1.0 mg/mL. The peptide fraction exhibits no cytotoxicity in both tumor and non-tumoral human cells at a concentration up to 0.3 mg/mL. Moreover, the peptide fraction presents anti-inflammatory activity, significantly reducing the expression of the TNFα gene by more than 29.7% in non-stimulated colon cells and by 50% in lipopolysaccharide-stimulated colon cells. It also inhibits the activity of the carbohydrate digestive enzymes α-amylase (IC50 of 199.3 ± 0.9 µg/mL) and α-glucosidase (IC20 of 270.6 ± 6.0 µg/mL). Overall, the findings showed that the peptide fraction exhibits antibacterial, antioxidant, anti-inflammatory, and antidiabetic activity. This study represents a step forward in the evaluation of the functional biological properties of S. cerevisiae bioactive peptides. Full article
(This article belongs to the Special Issue Microbial Natural Products as a Source of Novel Antimicrobials)
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20 pages, 8849 KiB  
Article
Rhamnolipid Nano-Micelles Inhibit SARS-CoV-2 Infection and Have No Dermal or Eye Toxic Effects in Rabbits
by Alaa M. Ali, Harriet J. Hill, Gehad E. Elkhouly, Marwa Reda Bakkar, Nermeen R. Raya, Zania Stamataki and Yasmin Abo-zeid
Antibiotics 2022, 11(11), 1556; https://doi.org/10.3390/antibiotics11111556 - 4 Nov 2022
Cited by 6 | Viewed by 2173
Abstract
Hand hygiene is considered to be the key factor in controlling and preventing infection, either in hospital care settings or in the community. Alcohol-based hand sanitizers are commonly used due to their rapid action and broad spectrum of microbicidal activity, offering protection against [...] Read more.
Hand hygiene is considered to be the key factor in controlling and preventing infection, either in hospital care settings or in the community. Alcohol-based hand sanitizers are commonly used due to their rapid action and broad spectrum of microbicidal activity, offering protection against bacteria and viruses. However, their frequent administration during COVID-19 pandemic was associated with serious hazards, such as skin toxicity, including irritation, skin dermatitis, skin dryness or cracking, along with peeling redness or itching, with the higher possibility of getting infections. Thus, there is a need to find alternative and novel approaches for hand sanitation. In our previous publications, we reported that rhamnolipids nano-micelles had a comparable antibacterial activity to alcohol-based hand sanitizer and a lower cytotoxicity against human dermal fibroblast cells. In the current study, we investigated the antiviral activity of rhamnolipids nano-micelles against SARS-CoV-2. There was no cytotoxic effect on Vero cells noted at the tested concentrations of rhamnolipids nano-micelles. The rhamnolipids nano-micelles solution at 20, 78, and 312 µg/mL all demonstrated a significant (p < 0.05) decrease of virus infectivity compared to the virus only and the blank vehicle sample. In addition, an acute irritation test was performed on rabbits to further ascertain the biosafety of rhamnolipids nano-micelles. In the eye and skin irritation tests, no degree of irritation was recorded after topical application of rhamnolipids nano-micelles. In addition, histopathological, biomarker, and hematological analyses from animals treated with rhamnolipids nano-micelles were identical to those recorded for untreated animal. From the above, we can conclude that rhamnolipids nano-micelles are a good candidate to be used as a hand sanitizer instead of alcohol-based hand sanitizers. However, they must still be tested in the future among healthcare workers (HCW) in a health care setting to ascertain their antimicrobial efficacy and safety compared to alcohol-based hand sanitizers. Full article
(This article belongs to the Special Issue Microbial Natural Products as a Source of Novel Antimicrobials)
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23 pages, 5352 KiB  
Article
Antibiofilm and Antivirulence Activities of Gold and Zinc Oxide Nanoparticles Synthesized from Kimchi-Isolated Leuconostoc sp. Strain C2
by Min-Gyun Kang, Fazlurrahman Khan, Du-Min Jo, DoKyung Oh, Nazia Tabassum and Young-Mog Kim
Antibiotics 2022, 11(11), 1524; https://doi.org/10.3390/antibiotics11111524 - 1 Nov 2022
Cited by 18 | Viewed by 2778
Abstract
The rapid emergence of antimicrobial resistance (AMR) among bacterial pathogens results in antimicrobial treatment failure and the high mortality rate associated with AMR. The application of nanoparticles synthesized from probiotics will be widely accepted due to their efficacy and biocompatibility in treating microbial [...] Read more.
The rapid emergence of antimicrobial resistance (AMR) among bacterial pathogens results in antimicrobial treatment failure and the high mortality rate associated with AMR. The application of nanoparticles synthesized from probiotics will be widely accepted due to their efficacy and biocompatibility in treating microbial infections in humans. The current work sought to isolate and identify lactic acid bacteria (LAB) from Kimchi. Based on 16S rRNA gene sequencing, the LAB isolate C2 was identified as a member of the genus Leuconostoc. The obtained supernatant from Leuconostoc sp. strain C2 was employed for the green synthesis of metal (AuNPs) and metal oxide (ZnONPs) nanoparticles. UV–vis absorption spectra, FTIR analysis, XRD, DLS, FE-TEM, and EDS mapping were used to fully characterize these C2-AuNPs and C2-ZnONPs. The C2-AuNPs were found to be spherical in shape, with a size of 47.77 ± 5.7 nm and zeta potential of −19.35 ± 0.67 mV. The C2-ZnONPs were observed to be rod-shaped and 173.77 ± 14.53 nm in size. The C2-ZnONPs zeta potential was determined to be 26.62 ± 0.35 mV. The C2-AuNPs and C2-ZnONPs were shown to have antimicrobial activity against different pathogens. Furthermore, these nanoparticles inhibited the growth of Candida albicans. The antibiofilm and antivirulence properties of these NPs against Pseudomonas aeruginosa and Staphylococcus aureus were thoroughly investigated. C2-AuNPs were reported to be antibiofilm and antivirulence against P. aeruginosa, whereas C2-ZnONPs were antibiofilm and antivirulence against both P. aeruginosa and S. aureus. Furthermore, these nanoparticles disrupted the preformed mature biofilm of P. aeruginosa and S. aureus. The inhibitory impact was discovered to be concentration-dependent. The current research demonstrated that C2-AuNPs and C2-ZnONPs exhibited potential inhibitory effects on the biofilm and virulence features of bacterial pathogens. Further studies are needed to unravel the molecular mechanism behind biofilm inhibition and virulence attenuation. Full article
(This article belongs to the Special Issue Microbial Natural Products as a Source of Novel Antimicrobials)
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Review

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22 pages, 1668 KiB  
Review
A Mini-Review of Anti-Listerial Compounds from Marine Actinobacteria (1990–2023)
by Siyanda S. Ngema and Evelyn Madoroba
Antibiotics 2024, 13(4), 362; https://doi.org/10.3390/antibiotics13040362 - 15 Apr 2024
Viewed by 1186
Abstract
Among the foodborne illnesses, listeriosis has the third highest case mortality rate (20–30% or higher). Emerging drug-resistant strains of Listeria monocytogenes, a causative bacterium of listeriosis, exacerbate the seriousness of this public health concern. Novel anti-Listerial compounds are therefore needed to combat [...] Read more.
Among the foodborne illnesses, listeriosis has the third highest case mortality rate (20–30% or higher). Emerging drug-resistant strains of Listeria monocytogenes, a causative bacterium of listeriosis, exacerbate the seriousness of this public health concern. Novel anti-Listerial compounds are therefore needed to combat this challenge. In recent years, marine actinobacteria have come to be regarded as a promising source of novel antimicrobials. Hence, our aim was to provide a narrative of the available literature and discuss trends regarding bioprospecting marine actinobacteria for new anti-Listerial compounds. Four databases were searched for the review: Academic Search Ultimate, Google Scholar, ScienceDirect, and South African Thesis and Dissertations. The search was restricted to peer-reviewed full-text manuscripts that discussed marine actinobacteria as a source of antimicrobials and were written in English from 1990 to December 2023. In total, for the past three decades (1990–December 2023), only 23 compounds from marine actinobacteria have been tested for their anti-Listerial potential. Out of the 23 reported compounds, only 2-allyoxyphenol, adipostatins E–G, 4-bromophenol, and ansamycins (seco-geldanamycin B, 4.5-dihydro-17-O-demethylgeldanamycin, and seco-geldanamycin) have been found to possess anti-Listerial activity. Thus, our literature survey reveals the scarcity of published assays testing the anti-Listerial capacity of bioactive compounds sourced from marine actinobacteria during this period. Full article
(This article belongs to the Special Issue Microbial Natural Products as a Source of Novel Antimicrobials)
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38 pages, 4147 KiB  
Review
Overview of Bioactive Fungal Secondary Metabolites: Cytotoxic and Antimicrobial Compounds
by Rafael Conrado, Tainah Colombo Gomes, Gabriella Sales Calaço Roque and Ana Olívia De Souza
Antibiotics 2022, 11(11), 1604; https://doi.org/10.3390/antibiotics11111604 - 11 Nov 2022
Cited by 30 | Viewed by 5483
Abstract
Microorganisms are known as important sources of natural compounds that have been studied and applied for different purposes in distinct areas. Specifically, in the pharmaceutical area, fungi have been explored mainly as sources of antibiotics, antiviral, anti-inflammatory, enzyme inhibitors, hypercholesteremic, antineoplastic/antitumor, immunomodulators, and [...] Read more.
Microorganisms are known as important sources of natural compounds that have been studied and applied for different purposes in distinct areas. Specifically, in the pharmaceutical area, fungi have been explored mainly as sources of antibiotics, antiviral, anti-inflammatory, enzyme inhibitors, hypercholesteremic, antineoplastic/antitumor, immunomodulators, and immunosuppressants agents. However, historically, the high demand for new antimicrobial and antitumor agents has not been sufficiently attended by the drug discovery process, highlighting the relevance of intensifying studies to reach sustainable employment of the huge world biodiversity, including the microorganisms. Therefore, this review describes the main approaches and tools applied in the search for bioactive secondary metabolites, as well as presents several examples of compounds produced by different fungi species with proven pharmacological effects and additional examples of fungal cytotoxic and antimicrobial molecules. The review does not cover all fungal secondary metabolites already described; however, it presents some reports that can be useful at any phase of the drug discovery process, mainly for pharmaceutical applications. Full article
(This article belongs to the Special Issue Microbial Natural Products as a Source of Novel Antimicrobials)
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