Chloroxylenol at environmental concentrations can promote conjugative transfer of antibiotic resistance genes by multiple mechanisms

The intergeneric conjugative transfer of antibiotic resistance genes (ARGs) is recognized as an important way to the dissemination of antibiotic resistance. However, it is unknown whether the extensive use of chloroxylenol (para-chloro-meta-xylenol, PCMX) in many pharmaceutical personal care products will lead to the spread of ARGs. In this study, the abilities and mechanisms of PCMX to accelerate the intergeneric conjugative transfer were investigated. Results showed that exposure of bacteria to environmental concentrations of PCMX (0.20-1.00 mg/L) can significantly stimulate the increase of conjugative transfer by 8.45-9.51 fold. The phenotypic experiments and genome-wide RNA sequencing revealed that 0.02-5.00 mg/L PCMX exposure could increase the content of alkaline phosphatase and malondialdehyde, which are characteristic products of cell wall and membrane damage. In addition, PCMX could lead to excessive production of reactive oxygen species (ROS) by 1.26-2.00 times, the superoxide dismutase and catalase produced by bacteria in response to oxidative stress were not enough to neutralize the damage of ROS, thus promoting the conjugative transfer. Gene Ontology enrichment analysis indicated that cell membrane permeability, pili, some chemical compounds transport and energy metabolism-affected conjugative transfer. This study deepened the understanding of PCMX in promoting propagation of ARGs, and provided new perspectives for use and treatment of personal care products. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

This study investigated the abilities and mechanisms of chloroxylenol (PCMX) in accelerating intergeneric conjugative transfer. The results showed that exposure to environmental concentrations of PCMX significantly increased the frequency of conjugative transfer. PCMX exposure induced damage to cell walls and membranes, resulting in excessive production of reactive oxygen species (ROS) and promoting conjugative transfer. Gene Ontology analysis revealed the impact of cell membrane permeability, pili, chemical compound transport, and energy metabolism on conjugative transfer.