Contribution of Endophytes for Combating Multi-Drug-Resistant Pathogens - A Recent Review on Novel Approaches

Multi-drug resistant (MDR) pathogens have become a major threat to global public health, largely due to the steadily declining efficacy of conventional antimicrobial therapies. In response, there is growing scientific interest in alternative and underexplored biological reservoirs capable of yielding novel antimicrobial leads. Among these, endophytes, which are microorganisms that colonize internal plant tissues without causing visible disease symptoms, are increasingly recognized for their remarkable biosynthetic potential and their ability to produce structurally diverse bioactive metabolites. In this review, we compile and critically discuss current evidence on endophytic diversity and the antimicrobial secondary metabolites produced by endophytes, with particular focus on their relevance in tackling antimicrobial resistance (AMR) and MDR infections. Recent advances reported during 2015–2025 has been highlighted, including the expanding catalogue of endophyte-derived antimicrobial scaffolds, their reported mechanisms of action and anti-virulence effects, and the contribution of emerging approaches such as genome mining, metabolomics-guided discovery, and synthetic biology in accelerating lead identification and validation. Collectively, the literature supports endophytes as a largely underutilized yet highly promising source of resistance-breaking antimicrobial candidates. Future efforts should prioritize mechanistic validation, reproducible cultivation and production strategies, and translational frameworks that can bridge the gap between experimental findings and clinical applicability.