MEDICINAL PLANT ENDOPHYTES AS A RESERVOIR OF NOVEL ANTIMICROBIAL AGENTS: RECENT ADVANCES, CHALLENGES, AND FUTURE PERSPECTIVES

AbstractEndophytes are microorganisms that colonize healthy plant tissues causing no visibleindications of disease and include a broad community of bacteria, fungi and actinomycetes.Medicinal plants are particularly valuable reservoirs of endophytes, as associated microbescan create structurally varied secondary metabolites with significant biological activity.Alkaloids, peptides, polyketides, terpenoids, steroids, quinones, flavonoids, phenoliccompounds and other chemical classes are represented among endophyte-derivedmetabolites. Many of these compounds have been reported to possess antibacterial andantifungal activity against pathogens of clinical and agricultural importance. A recentliterature review reported that from 2021 to 2024, 132 antibacterial metabolites fromendophytic fungi were reported, including the compounds active against methicillin-resistantStaphylococcus aureus, carbapenem-resistant Pseudomonas aeruginosa, and vancomycinresistant Enterococcus species.Traditional culture-dependent approaches are still crucial for the isolation of pure endophyticisolates, but they recover only a percentage of the microorganisms present within planttissues. Molecular methods such as 16S rRNA and ITS sequencing, metagenomics,metabolomics, genome mining and biosynthetic-gene analysis have enhanced the ability toexamine previously inaccessible microbial diversity and biosynthetic potential. Endophytesproduce antimicrobial chemicals that can act by membrane disruption, interfere with the cellwall, limit the synthesis of nucleic acids or proteins, inhibit enzymes, induce oxidative stress,and interfere with quorum sensing and biofilm formation. However, low metabolite yields,strain variability, rediscovery of known chemicals, toxicity, silent biosynthetic pathways andproblems associated with large-scale production remain important barriers. Futurecombination of genome mining, metabolomics, artificial intelligence, synthetic biology,optimal fermentation and microbial engineering could accelerate the discovery anddevelopment of endophyte-derived antimicrobial agents.