The persistence of plasmids in bacterial populations represents a puzzling evolutionary problem with serious clinical implications due to their role in the ongoing antibiotic resistance crisis. Recently, major advancements have been made towards resolving this 'plasmid paradox' but mainly in a non-clinical context. Here we propose an additional explanation for the maintenance of multidrug resistance (MDR) plasmids in clinical Escherichia coli strains. After co-evolving two MDR plasmids encoding last resort carbapenem resistance with an extraintestinal pathogenic E. coli strain, we observed that chromosomal media adaptive mutations in the global regulatory systems CCR (Carbon Catabolite Repression) and ArcAB (Aerobic Respiration Control) pleiotropically mitigated the costs of both plasmids. Mechanistically, cost reductions were due to a net downregulation of plasmid gene expression. Our results suggest that global chromosomal transcriptional re-wiring during bacterial niche-adaptation may facilitate plasmid maintenance.

中文翻译：

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n带生态位适应降低了多重耐药质粒的成本

质粒在细菌种群中的持久性代表着一个令人费解的进化问题，由于其在持续的抗生素耐药性危机中的作用，具有严重的临床意义。最近，在解决这种“质粒悖论”方面取得了重大进展，但主要是在非临床背景下。在这里，我们提出在临床大肠杆菌菌株中维持多药耐药性（MDR）质粒的另一种解释。在将两个编码最后手段碳青霉烯抗性的MDR质粒与肠外致病性大肠杆菌菌株共同进化后，我们观察到全球调节系统CCR（碳分解代谢抑制）和ArcAB（有氧呼吸控制）中的染色体培养基适应性突变多效性地降低了成本两种质粒。机械上，成本降低是由于质粒基因表达的净下调。我们的研究结果表明细菌利基适应过程中的全球染色体转录重新接线可能有助于质粒的维护。