Genetic Elements That Contribute to Antibiotic Resistance in Bacteria of Clinical Importance

Abstract

Antimicrobial resistance (AMR) poses a severe threat to global health by limiting treatment options and increasing clinical and economic burdens. This review synthesizes evidence showing that resistance evolution is strongly shaped by antibiotic pressure, leading to the accumulation of adaptive mutations, activation of efflux systems, and widespread dissemination of resistance determinants across clinical, animal, and environmental settings. We highlight recent genomic, metagenomic, and structural findings that elucidate the molecular basis of AMR, with particular emphasis on horizontal gene transfer mediated by mobile genetic elements such as plasmids, integrons, and transposons. Analyses across One Health interfaces reveal extensive sharing of antimicrobial resistance genes among humans, livestock, and environmental reservoirs, identifying Enterobacteriaceae and ESKAPE pathogens as key hubs of resistance dissemination. Special focus is placed on Acinetobacter baumannii, where phylogenetic and three-dimensional structural analyses of class D β-lactamases OXA-23 and OXA-24/40 demonstrate a conserved catalytic framework coupled with substantial sequence and conformational variability. These structural differences likely influence carbapenem specificity and resistance levels. Collectively, the findings underscore how genetic diversity, mobile elements, and structural adaptation converge to drive AMR, reinforcing the need for integrated genomic and structural approaches to guide surveillance and antimicrobial development.