College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, China.
Sci Total Environ. 2022 Mar 1;810:152245. doi: 10.1016/j.scitotenv.2021.152245. Epub 2021 Dec 9.
The rapid dissemination of antibiotic resistance by horizontal gene transfer (HGT) renders the global resistance crisis more tense and urgent as few effective antimicrobials are available to combat multidrug-resistant (MDR) pathogens at present. Conjugation is one of the most dominant and representative pathways of HGT. Antibiotic residue in environment is recognized as an important accelerator for conjugal transfer, whereas the roles of non-antibiotic pharmaceuticals in this process are not fully understood. Here we found that environmentally relevant concentrations of paclitaxel as well as its derivative docetaxel, two commonly used anticancer drugs, remarkably facilitated the conjugative transfer of resistance plasmids carrying multiple antibiotic resistance genes (ARGs). The underlying mechanisms accounting for the enhanced conjugation were investigated by detecting the activity of RpoS regulon, membrane permeability, SOS response and gene expression of conjugative transfer systems. Our results showed that paclitaxel induced a series of cellular responses, including up-regulation of rpoS expression, activated SOS response, increased cell membrane permeability, enhanced plasmid replication and mating pilus formation. Collectively, our data provide new insight on the roles of paclitaxel and its derivative in promoting the conjugal transfer of ARGs, highlighting the importance of good antimicrobial stewardship.
水平基因转移（HGT）导致抗生素耐药性的快速传播，使得全球耐药危机更加紧张和紧迫，因为目前几乎没有有效的抗菌药物来对抗多药耐药（MDR）病原体。 conjugation 是 HGT 最主要和最具代表性的途径之一。环境中的抗生素残留被认为是促进接合转移的重要因素，而环境中非抗生素药物在这一过程中的作用尚不完全清楚。在这里，我们发现环境相关浓度的紫杉醇及其衍生物多西紫杉醇，两种常用的抗癌药物，显著促进了携带多种抗生素耐药基因（ARGs）的抗性质粒的接合转移。通过检测 RpoS 调控子的活性、膜通透性、SOS 反应和接合转移系统的基因表达，研究了增强接合的潜在机制。我们的结果表明，紫杉醇诱导了一系列细胞反应，包括 rpoS 表达的上调、SOS 反应的激活、细胞膜通透性的增加、质粒复制和性菌毛形成的增强。总之，我们的数据提供了紫杉醇及其衍生物在促进 ARGs 接合转移中的作用的新见解，强调了良好的抗菌药物管理的重要性。
