Microbial Bioactives
Microbial Bioactives | Online ISSN 2209-2161
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Volume 9 Number 1 2026
REVIEWS (Open Access)
Reinventing Antibiotic Discovery in the Age of Antimicrobial Resistance: Emerging Sources, Novel Targets, and Post-Genomic Strategies
Gautam Kumar 1, Nileema S. Gore 2, Sankalp Misra 3
Microbial Bioactives 9 (1) 1-8 https://doi.org/10.25163/microbbioacts.9110610
Submitted: 15 October 2025 Revised: 10 January 2026 Accepted: 17 January 2026 Published: 19 January 2026
Abstract
Antimicrobial resistance (AMR) represents one of the most pressing global health crises of the twenty-first century, threatening the effectiveness of existing antibiotics and undermining decades of medical progress. Following the antibiotic “golden age” between 1940 and 1962, during which most clinically relevant antibiotic classes were discovered, the development pipeline has stagnated, yielding few truly novel agents. This systematic review and meta-analysis synthesize current evidence on emerging antimicrobial discovery strategies designed to overcome resistance by targeting novel bacterial pathways, harnessing underexplored microbial sources, and deploying advanced molecular and computational technologies. Literature published across microbiology, natural product chemistry, and drug discovery disciplines was systematically analyzed to evaluate efficacy trends, discovery success rates, and mechanistic innovation. Quantitative data on minimum inhibitory concentrations (MICs) and inhibitory concentrations (IC50) were meta-analyzed where comparable outcomes were available. The findings demonstrate that modern discovery efforts increasingly prioritize non-traditional targets such as cell membrane biogenesis, metal acquisition systems, quorum sensing pathways, and dormant-cell survival mechanisms. In parallel, genome mining, in situ cultivation, co-cultivation, and mechanism-guided screening have substantially improved access to previously cryptic biosynthetic gene clusters. Bioprospecting in extreme and underexplored environments, particularly marine and polar ecosystems, continues to yield chemically distinct compounds with potent activity against priority AMR pathogens, including ESKAPE organisms. Collectively, the evidence indicates that integrating novel targets with innovative discovery platforms offers a viable path forward to revitalize antibiotic development. This review underscores the necessity of a multifaceted discovery paradigm that re-centers natural products while leveraging post-genomic technologies to confront the escalating AMR crisis.
Keywords: antimicrobial resistance; antibiotic discovery; genome mining; natural products; novel drug targets; bioprospecting; biosynthetic gene clusters
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