The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
Cell Host Microbe. 2022 Jul 13;30(7):1034-1047.e6. doi: 10.1016/j.chom.2022.04.008. Epub 2022 May 10.
Large-scale genomic studies have identified within-host adaptation as a hallmark of bacterial infections. However, the impact of physiological, metabolic, and immunological differences between distinct niches on the pathoadaptation of opportunistic pathogens remains elusive. Here, we profile the within-host adaptation and evolutionary trajectories of 976 isolates representing 119 lineages of uropathogenic Escherichia coli (UPEC) sampled longitudinally from both the gastrointestinal and urinary tracts of 123 patients with urinary tract infections. We show that lineages persisting in both niches within a patient exhibit increased allelic diversity. Habitat-specific selection results in niche-specific adaptive mutations and genes, putatively mediating fitness in either environment. Within-lineage inter-habitat genomic plasticity mediated by mobile genetic elements (MGEs) provides the opportunistic pathogen with a mechanism to adapt to the physiological conditions of either habitat, and reduced MGE richness is associated with recurrence in gut-adapted UPEC lineages. Collectively, our results establish niche-specific adaptation as a driver of UPEC within-host evolution.
大规模基因组研究已经确定了宿主内适应是细菌感染的一个标志。然而，不同生态位之间的生理、代谢和免疫差异对机会性病原体的病理适应的影响仍然难以捉摸。在这里，我们对 976 个分离株进行了分析，这些分离株代表了从 123 名尿路感染患者的胃肠道和泌尿道中纵向采集的 119 个谱系的尿路致病性大肠杆菌 (UPEC)。我们表明，在一个患者体内同时存在于两个生态位中的谱系表现出更高的等位基因多样性。特定生态位的选择导致了生态位特异性的适应性突变和基因，这些突变和基因可能在任一环境中都有助于适应。通过移动遗传元件 (MGE) 介导的种内跨生态位基因组可塑性为机会性病原体提供了一种适应任一生态位生理条件的机制，而 MGE 丰富度的降低与肠道适应的 UPEC 谱系的复发有关。总的来说，我们的研究结果确立了特定生态位的适应是 UPEC 宿主内进化的驱动因素。
