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Endophytic Microorganisms as Sources of Antimicrobial Natural Products: Mechanisms of Action and Opportunities to Combat Antibiotic Resistance
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Behin Omidi   , Amirreza Rasoulian , Yasin SarveAhrabi * |
| Department of Biology, CT.C., Islamic Azad University, Tehran |
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Abstract: (7 Views) |
| Antimicrobial resistance (AMR) is increasingly compromising the effectiveness of conventional antimicrobial agents, highlighting the need to discover new bioactive compounds from underexplored biological sources. Endophytic microorganisms, which inhabit internal plant tissues, represent a promising reservoir of structurally diverse natural products with potential antimicrobial activity. This review examines the diversity of antimicrobial metabolites produced by endophytes, their mechanisms of action, and emerging strategies for discovering and developing compounds active against drug-resistant pathogens. A structured literature search of PubMed, Scopus, and Web of Science was conducted for studies published up to 2024, focusing on endophytic secondary metabolites, biosynthetic gene clusters, antimicrobial mechanisms, and genome-guided discovery approaches. Reported endophyte-derived compounds include polyketides, nonribosomal peptides, alkaloids, terpenoids, and phenolic compounds, some of which exhibit activity against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Emerging discovery strategies, including genome mining, bioinformatics, co-cultivation, and the one strain–many compounds (OSMAC) approach, have facilitated the identification of previously uncharacterized biosynthetic pathways and metabolites. Proposed antimicrobial mechanisms include membrane disruption, interference with quorum sensing, and enhancement of antibiotic activity through synergistic interactions. Despite their considerable potential, the development of endophyte-derived antimicrobials remains constrained by challenges such as low production yields, difficulties in cultivation, and the need for comprehensive efficacy and safety evaluation. Integrating genomics, metabolomics, and metabolic engineering may help overcome these limitations and accelerate the development of promising endophyte-derived compounds into potential therapeutic candidates. |
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| Keywords: Endophytic microorganisms, antimicrobial natural products, antimicrobial resistance, multidrug-resistant pathogens, secondary metabolites, genome mining, mechanisms of action |
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Type of Study: Research |
Subject:
General
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