Endophytic Fungal Secondary Metabolites as Potential Drug Discovery Agents against Antimicrobial Resistance: A Systematic Review

Introduction: The rise of antimicrobial resistance has become a pressing global public health concern, necessitating the exploration of alternative antimicrobial agents. Endophytes have been recognized as a rich source of novel metabolites with potential antimicrobial properties. Aim: To comprehensively review the literature on secondary metabolites from endophytic fungi with antimicrobial activities against priority pathogens. Method: A systematic search was conducted in four electronic databases: PubMed, Scopus, Web of Science, and Google Scholar. Studies that reported the isolation and elucidation of secondary endophyte metabolites with inhibitory effects against clinically relevant bacteria and fungi were included. The Newcastle–Ottawa scale (NOS) was used to evaluate the methodological quality of the included studies. Results: Twenty-one studies met the inclusion criteria, and 77 specialised metabolites were characterised across the studies. These secondary metabolites exhibited broad-spectrum in vitro growth inhibition against priority pathogens, including bacteria such as E. coli, Acinetobacter baumannii, and Pseudomonas aeruginosa, and fungi such as Candida albicans and Aspergillus spp. Conclusion: This systematic review provides an overview of the current evidence on secondary endophyte metabolites with antibacterial and antifungal activities. The results highlight the potential of endophytes as a source of new antimicrobial agents.