摘要
      抗生素抗性基因（ARGs）的属间偶联转移被认为是传播抗生素抗性的重要途径。然而，尚不清楚在许多个人护理药品中广泛使用氯二甲酚（对氯间二甲酚，PCMX）是否会导致ARGs的传播。在本研究中，研究了PCMX加速属间共轭转移的能力和机制。结果表明，细菌暴露于环境浓度的PCMX（0.20–1.00 mg/L）可显著刺激偶联转移增加8.45–9.51倍。表型实验和全基因组RNA测序显示，0.02–5.00 mg/L PCMX暴露可增加碱性磷酸酶和丙二醛的含量，这是细胞壁和膜损伤的特征产物。此外，PCMX可导致活性氧（ROS）的过量产生1.26–2.00倍，细菌在氧化应激时产生的超氧化物歧化酶和过氧化氢酶不足以中和ROS的损伤，从而促进结合转移。基因本体富集分析表明，细胞膜通透性、菌毛、某些化合物的转运和能量代谢影响了偶联转移。本研究加深了对PCMX促进ARGs传播的理解，并为个人护理产品的使用和治疗提供了新的视角。
Abstract
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.

https://www.sciencedirect.com/science/article/abs/pii/S0048969721066778