Molecular and environmental drivers of antimicrobial resistance: global epidemiology, resistome dynamics, and one health strategies.

Antimicrobial resistance (AMR) has evolved into a critical global health security challenge, threatening the effectiveness of modern medicine and increasing morbidity and mortality worldwide. This review integrates current evidence on the molecular and environmental drivers of AMR, alongside global epidemiological patterns, resistome dynamics, and one health-based intervention strategy. Recent surveillance data indicate that AMR contributes to approximately 4.7 million deaths annually, with the highest burden concentrated in low- and middle-income countries, where resistance rates in key pathogens such as Escherichia coli, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus remain alarmingly high. At the molecular level, AMR is driven primarily by horizontal gene transfer mediated by mobile genetic elements, including plasmids, integrons, and transposons, enabling rapid dissemination of multidrug resistance among clinically important pathogens, including critical high-risk threats and critical multidrug-resistant organisms. Environmental reservoirs, including wastewater effluents, agricultural runoff, soil, and hospital discharge systems, serve as major hotspots for the selection and amplification of resistance genes. These environments facilitate the evolution of environmental resistomes, in which subinhibitory antibiotic concentrations, heavy metals, and other pollutants exert strong coselective pressures. Additionally, biofilm formation, metabolic adaptation, and climate-related stressors further increase the persistence and spread of resistance determinants. The integration of genomic surveillance and metagenomic approaches have improved the understanding of resistome structure and transmission pathways, yet significant gaps remain in linking environmental and clinical datasets. To address these challenges, emerging One Health strategies emphasize coordinated interventions across the human, animal, and environmental sectors. Novel approaches such as antimicrobial stewardship, phage therapy, CRISPR-based antimicrobials, and AI-driven drug discovery are being explored alongside improved diagnostics and environmental control measures. Collectively, a cross-sectoral, integrated One Health framework is essential to mitigate the emergence of AMR and sustain antimicrobial efficacy globally.