Soil to host environmental determinants fueling horizontal gene transfer and global AMR dissemination.

Antimicrobial resistance poses a critical and escalating threat to global health, with horizontal gene transfer serving as a primary driver of resistance dissemination among microbial communities across diverse ecological niches. The three classical horizontal gene transfer mechanisms, including transformation, transduction, and conjugation, are complemented by supplementary routes involving outer membrane vesicles, gene transfer agents, and nanotubes. Both internal and external drivers synergistically influence horizontal gene transfer. Factors influencing the within-host microbiome include gut metabolites, antibiotic exposure, temperature fluctuations, and microplastic ingestion, while external environmental drivers such as antibiotic residues, heavy metals, agrochemicals, and micro/nano-plastics similarly enhance the mobility of antimicrobial resistance genes. The main mechanisms contributing to increased antimicrobial resistance gene transfer include elevated oxidative stress markers, altered membrane permeability, and stimulation of conjugation-related gene expression. The synergistic effects of these biotic and abiotic pressures have accelerated the co-selection of antimicrobial resistance genes and mobile genetic elements, intensifying the proliferation of antimicrobial resistance in both clinical and environmental reservoirs. Novel mitigation strategies such as conjugation inhibitors, bacteriophage-based interventions, and biochar amendments show promise in curbing horizontal gene transfer-mediated antimicrobial resistance; however, these approaches still lack insight into the intricate molecular mechanisms underlying horizontal gene transfer and often act non-specifically against different pathogens. Moreover, strategies utilizing biochar remain time-consuming and require further optimization. Overall, understanding the mechanistic interplay between environmental stressors and genetic exchange pathways is essential for developing sustainable interventions to counteract antimicrobial resistance. This review highlights the pressing need for integrated surveillance and ecological risk assessment to effectively manage the environmental aspects of antimicrobial resistance.