Unveiling medicinal plant endophytes as hidden allies in the fight against antimicrobial resistance

Abstract Antimicrobial resistance has become one of the most serious threats to global public health, substantially decreasing the efficacy of traditional antibiotics and raising the potential risk of treatment failure against multidrug-resistant microbial infections. The rising crisis has brought about an urgent need for the discovery of new, safe, stable, and sustainable antimicrobial agents. In this instance, endophytic microorganisms such as bacteria, actinomycetes, and fungi that reside in internal plant tissues without causing any harm to their host have gained significant attention as useful reservoirs of structurally varied bioactive compounds. In contrast to typical microbial sources, endophytes exhibit unique ecological interactions with medicinal and stress-tolerant plants, which facilitate the manufacture of rare secondary metabolites with substantial pharmacological potential. Recent studies have shown that endophytic fungi and actinomycetes produce a range of antimicrobial compounds, enzymes, peptides, alkaloids, terpenoids, and nanoparticle-mediated metabolites, which can act against multidrug-resistant bacteria and fungi through mechanisms including cell wall disruption, membrane damage, reactive oxygen species-mediated oxidative stress, and inhibition of essential cellular enzymes. Apart from antimicrobial activity, a number of endophyte-derived metabolites and nanoparticles have been found to have promising antioxidant, anticancer, antiviral, and anti-inflammatory properties with comparatively lower toxicity and fewer side effects in biological models. This review critically discusses the variety, ecological role, antimicrobial mechanisms, toxicity assessment, synthesis of nanoparticles, and therapeutic potential of endophytic bacteria in the fight against antimicrobial resistance. The study also emphasizes recent developments, current problems, and future translational prospects that make endophyte-based treatments viable alternatives to conventional antibacterial medicines.