New Natural Products as Candidates for the Discovery of Antimicrobial Drugs

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

Deadline for manuscript submissions: 15 November 2025 | Viewed by 7192

Special Issue Editors


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Department of Infectious Microbiology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Interests: cytotoxicity of drugs and drug-delivery systems; experimental chemotherapy; signal transduction; pharmacodynamics
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Guest Editor
Department of Infectious Microbiology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria
Interests: pathogenic bacteria; food-borne zoonozes; virulence factors; bacteria–host relationships; infectious immunology; molecular biology; ecology of pathogens; new antibacterial agents; antimicrobial resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antimicrobial resistance has emerged as a global public health threat in recent decades due to the increasing number of microorganisms with resistance to one or more antimicrobial agents. Therefore, nowadays, there is an urgent need to find and develop new antimicrobial compounds of natural origin to fight life-threatening bacterial, fungal, and viral infections. Moreover, another equally important objective is to determine the ability of these pathogens to develop resistance against currently used treatment strategies and suggest therapeutic regimens to overcome resistance or new targeted therapies. Currently, antibiotics and antimicrobial chemotherapeutics comprise the main anti-infective strategy for patients in infectious, trauma, intensive care units. Unfortunately, their effectiveness is decreasing across the globe due to the global emergence of multi-drug-resistant (MDR) bacterial pathogens, turning bacterial infections into a serious concern. The prevention of the MDR pathogens that are spreading across healthcare facilities also remains a huge challenge because these microorganisms represent a serious cause of healthcare-associated infections.

This Special Issue will focus on new, safe, and effective antimicrobial products/compounds of plant, microbial, and animal origin, including different compounds, such as triterpenoids, alkaloids, phenols, flavonoids, antimicrobial peptides, metalloantibiotics, bacteriocins, and efflux pump inhibitors. We welcome all studies on the following:

  • Production, isolation, phytochemical characterization, and in vitro/in vivo activity of new natural metabolites with antimicrobial activity;
  • Pharmacodynamics and pharmacokinetics of known and new natural metabolites possessing antimicrobial activity;
  • Discovery of new antimicrobial targets in resistant microorganisms and ways for their inhibition;
  • Drug–drug interactions between natural products/compounds and clinically applied antibiotics for overcoming antimicrobial resistance in resistant and MDR microorganisms;
  • Improvement in antimicrobial potential and the bioavailability of known and new antimicrobial compounds of natural origin through different nanodelivery systems;
  • In vitro and in vivo toxicological evaluations of new antimicrobial compounds of natural origin and possibilities for the reduction of toxicity;
  • Natural agents for the microbial decontamination of healthcare surfaces, food contact materials, and other occupational, industrial, and domestic applications.

Prof. Dr. Maya Zaharieva
Prof. Dr. Hristo Najdenski
Guest Editors

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Keywords

  • natural products
  • antimicrobial mechanisms and strategies
  • combination effects
  • clinical applicability
  • in silico, in vitro and in vivo models
  • infection control

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Published Papers (4 papers)

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Research

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18 pages, 6332 KiB  
Article
Synergistic Antibacterial Effect of Mucus Fraction from Cornu aspersum and Cirpofloxacin Against Pathogenic Bacteria Isolated from Wounds of Diabetic Patients
by Mila Dobromirova Kaleva, Momchil Kermedchiev, Lyudmila Velkova, Maya Margaritova Zaharieva, Aleksandar Dolashki, Maria Todorova, Maya Guncheva, Pavlina Dolashka and Hristo Miladinov Najdenski
Antibiotics 2025, 14(3), 260; https://doi.org/10.3390/antibiotics14030260 - 4 Mar 2025
Cited by 1 | Viewed by 832
Abstract
Background/Objectives: The treatment of diabetic foot ulcers (DFU) is a challenging medical problem of extreme clinical and social importance, as a consequence of the emerging antibiotic resistance and decreased quality of life of diabetic patients due to impaired wound healing. One of [...] Read more.
Background/Objectives: The treatment of diabetic foot ulcers (DFU) is a challenging medical problem of extreme clinical and social importance, as a consequence of the emerging antibiotic resistance and decreased quality of life of diabetic patients due to impaired wound healing. One of the current trends in world science is the search for biologically active substances derived from living organisms. Biologically active peptides from snail mucus attract considerable scientific interest because of their pleiotropic pharmacological properties. The aim of our study was to evaluate the activity of a combination between a snail mucus protein fraction (MW > 20 kDa) obtained from the garden snail Cornu aspersum and the clinically applied antibacterial chemotherapeutic ciprofloxacin on pathogenic bacterial strains isolated from DFU. Results: The test bacterial strains were characterized as multidrug resistant. The combination between ciprofloxacin and the snail mucus fraction of interest led to additive or synergistic effects depending on the test strain. The mucus fraction exerted a well-pronounced wound-healing effect and no cytotoxicity on normal human fibroblasts and keratinocytes. Methods: The snail mucus was obtained by a patented technology (BG Utility model 2097/2015) and its electrophoretic profile was presented by SDS-PAGE. The bacterial strains were identified and tested for antimicrobial susceptibility (BD Phoenix M50 and Kirby–Bauer assay). The in vitro cytotoxicity of the mucus was evaluated by ISO 10995-5. The antimicrobial activity and combination effects were tested through ISO 20776/1 and the Checkerboard assay. Conclusions: The obtained results are promising and open new horizons for the development of novel combination treatment schemas for healing of infected DFU. Full article
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13 pages, 1391 KiB  
Article
Antimicrobial, Anti-Biofilm, Anti-Quorum Sensing and Cytotoxic Activities of Thymbra spicata L. subsp. spicata Essential Oils
by Timur Hakan Barak, Mujde Eryilmaz, Basar Karaca, Huseyin Servi, Simge Kara Ertekin, Muhittin Dinc and Hatice Ustuner
Antibiotics 2025, 14(2), 181; https://doi.org/10.3390/antibiotics14020181 - 11 Feb 2025
Cited by 2 | Viewed by 953
Abstract
Background/Objectives: Essential oils of Thymbra spicata subsp. spicata are known for their rich phytochemical content and bioactive properties. This study aimed to evaluate the antimicrobial, anti-biofilm and anti-quorum sensing, as well as the cytotoxic activities of T. spicata subsp. spicata essential oils (TS-EO1 [...] Read more.
Background/Objectives: Essential oils of Thymbra spicata subsp. spicata are known for their rich phytochemical content and bioactive properties. This study aimed to evaluate the antimicrobial, anti-biofilm and anti-quorum sensing, as well as the cytotoxic activities of T. spicata subsp. spicata essential oils (TS-EO1 and TS-EO2) obtained from two different localities in Türkiye, along with a detailed chemical composition analysis. Methods: TS-EO1 and TS-EO2 were obtained by the hydrodistillation method and analyzed using Gas Chromatography—Mass Spectrometry (GC-MS) to determine their phytochemical profiles. Antimicrobial activities were assessed against Gram-positive and Gram-negative bacteria, and fungal strains were assessed using the broth microdilution method. Anti-biofilm and anti-quorum sensing activities were evaluated using Pseudomonas aeruginosa PAO1 and Chromobacterium violaceum ATCC 12472, respectively. Cytotoxic properties were tested on four cell lines (A549, MCF-7, U87MG, and L929) using the MTT assay. Results: Both essential oil samples were rich in carvacrol (54.3% and 54.1%), followed by p-cymene and γ-terpinene. The essential oils exhibited significant antimicrobial activity, particularly against Staphylococcus aureus (6.25 mg/mL) and Candida parapsilosis (0.20 mg/mL). Sub-MIC concentrations significantly inhibited biofilm formation and quorum sensing. Both samples showed moderate cytotoxic properties against human cancer cell lines, particularly A549 (IC50: 116.3 and 134.4 μg/mL, respectively). Conclusions: This study showed that T. spicata subsp. spicata essential oils have significant antimicrobial, anti-biofilm, and anti-quorum sensing properties against various bacteria and fungi, along with moderate cytotoxic effects, indicating their medicinal and pharmaceutical potentials. This is the first study which revealed anti-biofilm and anti-quorum sensing properties of T. spicata essential oils to our knowledge. Full article
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25 pages, 16929 KiB  
Article
Potential Antimicrobial and Cytotoxic Activity of Caralluma indica Seed Extract
by Shunmuga Vadivu Ramalingam, Senthil Bakthavatchalam, Karnan Ramachandran, Vasthi Gnanarani Soloman, Afrin Khan Ajmal, Mohammad Khalid Al-Sadoon and Ramachandran Vinayagam
Antibiotics 2024, 13(12), 1193; https://doi.org/10.3390/antibiotics13121193 - 7 Dec 2024
Viewed by 1296
Abstract
Background: Plant-derived phytochemicals are crucial in fighting bacterial infections and in cancer therapy. Objective: This study investigates the phytochemical composition of the ethanolic extract obtained from Caralluma indica (C. indica) seeds and assesses its antimicrobial, anticancer, and antioxidant activities. Results: GC-MS [...] Read more.
Background: Plant-derived phytochemicals are crucial in fighting bacterial infections and in cancer therapy. Objective: This study investigates the phytochemical composition of the ethanolic extract obtained from Caralluma indica (C. indica) seeds and assesses its antimicrobial, anticancer, and antioxidant activities. Results: GC-MS analysis found 30 phytochemicals in C. indica seeds, including 5 bioactive compounds that have been shown to have antioxidant, antimicrobial, and cytotoxicity properties, through in silico evaluation. Phytochemical screening of C. indica identified and measured the phenolic compounds, providing insight into its bioactive potential and therapeutic properties. C. indica exhibited robust antioxidant capacity (DPPH, ABTS, nitric oxide, and H2O2 radical scavenging) alongside potent antimicrobial activity against oral pathogen and cytotoxicity activity on a human oral squamous carcinoma cell line (OECM-1) (EC50 of 169.35 µg/mL) and yeast cell Saccharomyces cerevisiae (215.82 µg/mL), with a selective index of 1.27. The subminimum % MBC/MFC of C. indica significantly reduced biofilm formation against oral pathogens (p < 0.05). Molecular docking studies showed a strong correlation (r = 0.862) between antifungal and anticancer targets, suggesting that the antimicrobial agents in C. indica contribute to cancer prevention mechanisms. Conclusions: These findings propose C. indica seeds as promising candidates for combating oral pathogens, inhibiting biofilm formation, and reducing the risk of oral cancer progression. Full article
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Review

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29 pages, 859 KiB  
Review
Honey as a Natural Antimicrobial
by Matthew Chidozie Ogwu and Sylvester Chibueze Izah
Antibiotics 2025, 14(3), 255; https://doi.org/10.3390/antibiotics14030255 - 1 Mar 2025
Cited by 1 | Viewed by 3550
Abstract
Honey, a natural product with a rich history of medicinal use, has gained increasing recognition for its potent antimicrobial properties, particularly against antibiotic-resistant pathogens. This review focuses on the antimicrobial mechanisms of honey, including its efficacy against resistant bacteria, such as Methicillin-resistant Staphylococcus [...] Read more.
Honey, a natural product with a rich history of medicinal use, has gained increasing recognition for its potent antimicrobial properties, particularly against antibiotic-resistant pathogens. This review focuses on the antimicrobial mechanisms of honey, including its efficacy against resistant bacteria, such as Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. The antimicrobial action of honey is multifactorial, involving hydrogen peroxide production, phenolic compounds, high sugar concentrations, and the presence of bee defensin-1. The composition of honey varies based on its floral source, which can influence its antimicrobial strength. Certain types, such as Manuka honey, are particularly effective in clinical applications due to their higher levels of bioactive compounds. Honey has also been shown to disrupt bacterial biofilms, a major factor in antibiotic resistance, enhancing its therapeutic potential in treating chronic wounds and infections, especially in patients with compromised immune systems. Moreover, honey’s ability to improve wound healing, reduce inflammation, and promote tissue regeneration highlights its broad therapeutic profile. As antibiotic resistance continues to challenge modern healthcare, honey offers a promising complementary treatment in antimicrobial therapy. Research into its specific bioactive components and potential synergistic effects with other natural agents, like ginger and propolis, could expand its applications. Standardizing honey products for medical use and establishing clinical guidelines are essential for optimizing its therapeutic benefits. As scientific understanding of honey’s antimicrobial mechanisms deepens, its integration into healthcare systems as an adjunct therapy is expected to increase, offering a natural and effective alternative in the fight against infectious diseases. Full article
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