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Genome Dynamics of Escherichia coli during Antibiotic Treatment: Transfer Loss and Persistence of Genetic Elements In situ of the Infant Gut

机译:抗生素治疗过程中大肠杆菌的基因组动力学:婴儿肠道原位遗传元件的转移丢失和持续存在

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摘要

Elucidating the adaptive strategies and plasticity of bacterial genomes in situ is crucial for understanding the epidemiology and evolution of pathogens threatening human health. While much is known about the evolution of Escherichia coli in controlled laboratory environments, less effort has been made to elucidate the genome dynamics of E. coli in its native settings. Here, we follow the genome dynamics of co-existing E. coli lineages in situ of the infant gut during the first year of life. One E. coli lineage causes a urinary tract infection (UTI) and experiences several alterations of its genomic content during subsequent antibiotic treatment. Interestingly, all isolates of this uropathogenic E. coli strain carried a highly stable plasmid implicated in virulence of diverse pathogenic strains from all over the world. While virulence elements are certainly beneficial during infection scenarios, their role in gut colonization and pathogen persistence is poorly understood. We performed in vivo competitive fitness experiments to assess the role of this highly disseminated virulence plasmid in gut colonization, but found no evidence for a direct benefit of plasmid carriage. Through plasmid stability assays, we demonstrate that this plasmid is maintained in a parasitic manner, by strong first-line inheritance mechanisms, acting on the single-cell level, rather than providing a direct survival advantage in the gut. Investigating the ecology of endemic accessory genetic elements, in their pathogenic hosts and native environment, is of vital importance if we want to understand the evolution and persistence of highly virulent and drug resistant bacterial isolates.
机译:阐明细菌基因组的适应性策略和可塑性,对于了解威胁人类健康的病原体的流行病学和进化至关重要。尽管人们对受控实验室环境中大肠杆菌的进化知之甚少,但人们为阐明大肠杆菌天然环境中的基因组动力学所做的努力却很少。在这里,我们跟踪婴儿肠道在生命的第一年中原位共存的大肠杆菌谱系的基因组动力学。一种大肠杆菌谱系会引起尿路感染(UTI),并在随后的抗生素治疗中经历其基因组含量的若干变化。有趣的是,该泌尿致病性大肠杆菌菌株的所有分离物均携带高度稳定的质粒,与来自世界各地的多种致病菌株的毒力有关。尽管毒力元素在感染过程中肯定是有益的,但人们对它们在肠道定植和病原体持久性中的作用了解甚少。我们进行了体内竞争适应性实验,以评估这种高度分散的毒力质粒在肠道菌落中的作用,但没有发现质粒运输直接受益的证据。通过质粒稳定性测定,我们证明了该质粒通过强大的一线遗传机制以寄生方式维持,作用于单细胞水平,而不是在肠道中提供直接的生存优势。如果我们想了解高毒力和耐药性细菌分离株的进化和持久性,研究其病原宿主和自然环境中的地方性辅助遗传元素的生态至关重要。

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