Multilayered molecular mechanisms and regulatory networks of aminoglycoside resistance in Enterobacteriaceae.

Enterobacteriaceae, as common clinical pathogens, pose a significant threat to global public health because of the infections they cause. Aminoglycoside antibiotics are critical for treating these infections; however, increasing antimicrobial resistance severely limits their clinical efficacy. This review provides a synthesis of the molecular mechanisms underlying aminoglycoside resistance in Enterobacteriaceae, including the roles of aminoglycoside-modifying enzymes, high-level resistance mediated by 16S rRNA methylation, alterations in bacterial membrane permeability, and heteroresistance. These resistance mechanisms are typically mediated by mobile genetic elements such as plasmids and integrons, facilitating rapid dissemination among bacterial strains. This review aims to provide a theoretical foundation for optimizing clinical antimicrobial strategies, developing novel therapeutic agents, and establishing effective surveillance frameworks.