The resistance of Salmonella enterica serovar Typhimurium to zinc oxide nanoparticles

Zinc oxide nanoparticles (ZnO NPs) serve as promising antibiotic alternatives owing to their exceptional antibacterial properties. However, it is inconclusive whether bacteria can develop resistance to ZnO NPs under chronic exposure. In this study, we identified an acquired and irreversible resistance to sublethal concentrations of ZnO NPs, but not to Zn (II) ions, in a strain of Salmonella enterica serovar Typhimurium CVCC541 (S. Typhimurium) following prolonged exposure. Whole-population genome sequencing authenticated a phoQ mutation pertained to this heritable resistance. The phoQ G33A mutation was accompanied by a downregulation of phoQ expression, triggering a remodeling of the outer membrane (characterized by increased production of OmpF and lipopolysaccharides, as well as altered lipid properties) and enhanced biofilm formation. Accordingly, we propose that S. Typhimurium adapts to ZnO NPs exposure by fortifying its outer membrane and biofilm, thereby evolving resistance. Our findings provide an innovative paradigm for an in-depth knowledge of the antimicrobial resistance crisis.