Low concentration quaternary ammonium compounds promoted antibiotic resistance gene transfer via plasmid conjugation

During the pandemic of COVID-19, the amounts of quaternary ammonium compounds (QACs) used to inactivate the virus in public facilities, hospitals and households increased, which raised concerns about the evolution and transmis-sion of antimicrobial resistance (AMR). Although QACs may play an important role in the propagation of antibiotic re-sistance gene (ARGs), the potential contribution and mechanism remains unclear. Here, the results showed that benzyl dodecyl dimethyl ammonium chloride (DDBAC) and didecyl dimethyl ammonium chloride (DDAC) significantly pro-moted plasmid RP4-mediated ARGs transfer within and across genera at environmental relevant concentrations (0.0004-0.4 mg/L). Low concentrations of QACs did not contribute to the permeability of the cell plasma membrane, but significantly increased the permeability of the cell outer membrane due to the decrease in content of lipopolysac-charides. QACs altered the composition and content of extracellular polymeric substances (EPS) and were positively correlated with the conjugation frequency. Furthermore, transcriptional expression levels of genes encode for mating pairing formation (trbB), DNA replication and translocation (trfA), and global regulators (korA, korB, trbA) are regu-lated by QACs. And we demonstrate for the first time that QACs decreased the concentration of extracellular AI-2 sig-nals, which was verified to be involved in regulating conjugative transfer genes (trbB, trfA). Collectively, our findings underscore the risk of increased disinfectant concentrations of QACs on the ARGs transfer and provide new mecha-nisms of plasmid conjugation.

Automated summary

During the pandemic of COVID-19, the increased use of quaternary ammonium compounds (QACs) for virus inactivation raised concerns about the evolution and transmission of antimicrobial resistance (AMR). This study investigated the potential contribution and mechanism of QACs in the propagation of antibiotic resistance genes (ARGs). The results showed that certain QACs promoted the transfer of ARGs within and across genera at environmentally-relevant concentrations. QACs altered the membrane permeability and composition of extracellular polymeric substances (EPS), which were correlated with the conjugation frequency.