The biological features that allow a pathogen to survive in the hospital environment are mostly unknown. The extinction of bacterial epidemics in hospitals is mostly attributed to changes in medical practice, including infection control, but the role of bacterial adaptation has never been documented. We analysed a collection of Pseudomonas aeruginosa isolates belonging to the Besançon Epidemic Strain (BES), responsible for a 12year nosocomial outbreak, using a genotype-to-phenotype approach. Bayesian analysis estimated the emergence of the clone in the hospital 5 years before its opening, during the creation of its water distribution network made of copper. BES survived better than the reference strains PAO1 and PA14 in a copper solution due to a genomic island containing 13 metal-resistance genes and was specifically able to proliferate in the ubiquitous amoeba Vermamoeba vermiformis. Mutations affecting amino-acid metabolism, antibiotic resistance, lipopolysaccharide biosynthesis, and regulation were enriched during the spread of BES. Seven distinct regulatory mutations attenuated the overexpression of the genes encoding the efflux pump MexAB-OprM over time. The fitness of BES decreased over time in correlation with its genome size. Overall, the resistance to inhibitors and predators presumably aided the proliferation and propagation of BES in the plumbing system of the hospital. The pathogen further spread among patients via multiple routes of contamination. The decreased prevalence of patients infected by BES mirrored the parallel and convergent genomic evolution and reduction that affected bacterial fitness. Along with infection control measures, this may have participated in the extinction of BES in the hospital setting.

中文翻译：

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铜绿假单胞菌地方性谱系在医院的兴衰

使病原体在医院环境中存活的生物学特征大多是未知的。医院中细菌流行病的灭绝主要归因于医疗实践的变化，包括感染控制，但从未记录过细菌适应的作用。我们分析了一组铜绿假单胞菌 使用基因型到表型的方法，属于贝桑松流行菌株 (BES) 的分离株，负责 12 年的医院暴发。贝叶斯分析估计，在医院开业前 5 年，在创建由铜制成的配水网络期间，该医院出现了克隆。由于含有 13 个金属抗性基因的基因组岛，BES 在铜溶液中比参考菌株 PAO1 和 PA14 存活得更好，并且特别能够在无处不在的变形虫Vermamoeba vermiformis中增殖. 在 BES 的传播过程中，影响氨基酸代谢、抗生素耐药性、脂多糖生物合成和调控的突变得到了丰富。随着时间的推移，七种不同的调节突变减弱了编码外排泵 MexAB-OprM 的基因的过度表达。BES 的适应度随着时间的推移而下降，与其基因组大小相关。总体而言，对抑制剂和捕食者的抵抗力可能有助于 BES 在医院管道系统中的增殖和传播。病原体通过多种污染途径在患者之间进一步传播。受 BES 感染的患者患病率下降反映了影响细菌适应性的平行且趋同的基因组进化和减少。与感染控制措施一起，这可能参与了 BES 在医院环境中的灭绝。