Role of extended-spectrum β-lactamase (ESBL) genes in the dissemination of β-lactam resistance within aquatic environments: mechanisms, persistence, and one health implications.

Antimicrobial resistance of pathogenic bacteria has rapidly increased over the past 20 years, creating a major global health threat. Extended-spectrum β-lactamases (ESBLs) are major drivers of resistance to β-lactam antibiotics, hydrolyzing broad-spectrum cephalosporines and monobactams. ESBL-producing Enterobacteriaceae are widespread across aquatic environments. While previous reviews have broadly described clinical ESBL epidemiology, a comprehensive synthesis explicitly linking aquatic microenvironmental niches, mobile genetic element dynamics, and environmental selection mechanisms remains lacking. This review addresses this gap by critically evaluating how aquatic environments function as active evolutionary reactors rather than mere passive sinks. The dissemination of these ESBL genes depends on conjugative plasmids, insertion sequences, and transposons. Specifically, insertion sequence ISEcp1 mobilizes and enhances the expression of blaCTX-M genes through transposition and strong promoter activity, while IS26 promotes the capture, rearrangement and accumulation of multi-drug resistance determinants within plasmids and transposons. ESBL genes persist in both intracellular and extracellular forms within sediments, biofilms, and microplastic-associated habitats. This review describes the prevalence, mobility, dissemination mechanisms, and environmental-clinical connectivity of ESBL determinants in aquatic systems.