摘要
      抗生素抗性基因（ARGs）由于其广泛存在和跨越物种边界传播的显著能力而引起了人们的极大关注。质粒携带促进ARGs在环境中的持久性和传播。为了研究质粒的流行率，我们在环境相关浓度的四环素（TC）存在下，用耐多药质粒RP4:：gfp对恶臭假单胞菌KT2442进行了连续传代实验。结果表明，环境浓度中的TC补偿了质粒带来的适应度成本，延长了携带质粒菌株的持续时间，并在质粒丢失的窗口时间后诱导质粒的再次出现。转录组测序表明，乙醛酸分流的上调和核糖体生物合成的下调补偿了质粒的恢复。因此，假设在环境相关浓度的TC存在的情况下，转录修饰可以增强抗性质粒在群体中的持久性。这项工作为开发一种基于质粒丢失窗口时间的技术开辟了一条途径，以防止ARGs的传播。
Abstract
Antibiotic resistance genes (ARGs) have captured immense attention due to their widespread existence and remarkable ability to spread across species boundaries. Plasmid carriage promotes the persistence and spread of ARGs in the environment. To investigate the prevalence of plasmids, we conducted serial passage experiments on Pseudomonas putida KT2442 with multidrug-resistant plasmid RP4::gfp in the presence of tetracycline (TC) in an environmentally relevant concentration. The results showed that TC in environmental concentration compensated the fitness cost brought by the plasmid, prolonged the persistence time of the plasmid-bearing strain, and induced the reoccurrence of plasmids after the window time of plasmid loss. Transcriptome sequencing showed that plasmid recovery was compensated by the up-regulation of glyoxylic acid shunt and the down-regulation of ribosome biosynthesis. It is therefore hypothesized that transcriptional modifications may enhance the persistence of resistant plasmids within the population in the presence of TC in an environmentally relevant concentration. This work opens up an avenue for developing a technology based on the window time of plasmid loss to prevent the spread of ARGs.

https://www.sciencedirect.com/science/article/abs/pii/S0048969723022210