Subinhibitory Concentrations of Disinfectants Promote the Horizontal Transfer of Multidrug Resistance Genes within and across Genera

The greater abundances of antibiotic resistance genes (ARGs) in point-of-use tap and reclaimed water than that in freshly treated water raise the question whether residual disinfectants in distribution systems facilitate the spread of ARGs. This study investigated three widely used disinfectants (free chlorine, chloramine, and hydrogen peroxide) on promoting ARGs transfer within Escherichia coli strains and across genera from Escherichia coli to Salmonella typhimurium. The results demonstrated that subinhibitory concentrations (lower than minimum inhibitory concentrations [MICs]) of these disinfectants, namely 0.1-1 mg/L Cl₂ for free chlorine, 0.1-1 mg/L Cl₂ for chloramine, and 0.24-3 mg/L H₂O₂, led to concentration-dependent increases in intragenera conjugative transfer by 3.4-6.4, 1.9-7.5, and 1.4-5.4 folds compared with controls, respectively. By comparison, the intergenera conjugative frequencies were slightly increased by approximately 1.4-2.3 folds compared with controls. However, exposure to disinfectants concentrations higher than MICs significantly suppressed conjugative transfer. This study provided evidence and insights into possible underlying mechanisms for enhanced conjugative transfer, which involved intracellular reactive oxygen species formation, SOS response, increased cell membrane permeability, and altered expressions of conjugation-relevant genes. The results suggest that certain oxidative chemicals, such as disinfectants, accelerate ARGs transfer and therefore justify motivations in evaluating disinfection alternatives for controlling antibiotic resistance. This study also triggers questions regarding the potential role of environmental chemicals in the global spread of antibiotic resistance.