摘要
      抗微生物耐药性一直被认为是对生物安全和人类健康的巨大威胁。而抗生素抗性基因（ARGs）通过结合质粒的传播是抗生素耐药性流行的关键因素。对乙酰氨基酚（PRC）是一种非鸦片类镇痛药，是一种在世界范围内广泛使用的解热和轻度镇痛药，可用于多种处方。目前尚不清楚中华人民共和国是否能促进ARGs的传播。在这里，证明了PRC在已建立的缀合模型中促进了属间缀合质粒的转移。PRC处理的供体和受体菌株都出现了活性氧（ROS）、SOS反应和细胞膜通透性的变化。相应地，转录组分析显示，PRC暴露后，参与细胞膜通透性和SOS反应的基因表达显著上调。更直接的是，PRC还增加了供体中trbG和trbP结合相关基因的表达。本研究首次证明PRC可以促进属间结合质粒的转移。总的来说，这些发现表明了与非抗生素物质PRC的存在相关的潜在威胁，这可以为抗菌药物耐药性的传播提供重要的见解。
Abstract
Antimicrobial resistance has been considered as a great threat to biosecurity and human health. And the transmission of antibiotic resistance genes (ARGs) by conjugated plasmid is a key factor in the prevalence of antimicrobial resistance. Paracetamol (PRC), one of nonopioid analgesics, is an extensively used antipyretic and mild analgesic worldwide available for numerous prescriptions. It was unclear whether PRC could promote the spread of ARGs. Here, it was demonstrated that PRC promoted intergenera conjugative plasmid transfer in an established conjugation model. Both donor and recipient strains treated by PRC emerged the variations of reactive oxygen species (ROS), SOS response and cell membrane permeability. Correspondingly, transcriptome analysis revealed that the gene expression involved in cell membrane permeability and SOS response was up-regulated significantly after PRC exposure. More directly, PRC also increased the expressions of conjugation related genes of trbG and trbP in donor. This study proved for the first time that PRC could enhance the intergenera conjugative plasmid transfer. Collectively, these findings manifested the potential threat associated with the existence of non-antibiotic substance PRC, which could provide an important insight into antimicrobial resistance spread.

https://www.sciencedirect.com/science/article/abs/pii/S0013935122015900