The bacterial genetic determinants of Escherichia coli capacity to cause bloodstream infections in humans.

IF 4.5 2区 生物学 Q1 Agricultural and Biological Sciences PLoS Genetics Pub Date : 2023-08-02 eCollection Date: 2023-08-01 DOI:10.1371/journal.pgen.1010842
Judit Burgaya, Julie Marin, Guilhem Royer, Bénédicte Condamine, Benoit Gachet, Olivier Clermont, Françoise Jaureguy, Charles Burdet, Agnès Lefort, Victoire de Lastours, Erick Denamur, Marco Galardini, François Blanquart
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Abstract

Escherichia coli is both a highly prevalent commensal and a major opportunistic pathogen causing bloodstream infections (BSI). A systematic analysis characterizing the genomic determinants of extra-intestinal pathogenic vs. commensal isolates in human populations, which could inform mechanisms of pathogenesis, diagnostic, prevention and treatment is still lacking. We used a collection of 912 BSI and 370 commensal E. coli isolates collected in France over a 17-year period (2000-2017). We compared their pangenomes, genetic backgrounds (phylogroups, STs, O groups), presence of virulence-associated genes (VAGs) and antimicrobial resistance genes, finding significant differences in all comparisons between commensal and BSI isolates. A machine learning linear model trained on all the genetic variants derived from the pangenome and controlling for population structure reveals similar differences in VAGs, discovers new variants associated with pathogenicity (capacity to cause BSI), and accurately classifies BSI vs. commensal strains. Pathogenicity is a highly heritable trait, with up to 69% of the variance explained by bacterial genetic variants. Lastly, complementing our commensal collection with an older collection from 1980, we predict that pathogenicity continuously increased through 1980, 2000, to 2010. Together our findings imply that E. coli exhibit substantial genetic variation contributing to the transition between commensalism and pathogenicity and that this species evolved towards higher pathogenicity.

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大肠杆菌导致人类血液感染的细菌基因决定因素。
大肠埃希菌既是一种高发的共生菌,也是引起血流感染(BSI)的主要机会性病原体。目前仍缺乏对人类肠道外致病性与共感性分离菌基因组决定因素的系统分析,而这些分析可为发病机制、诊断、预防和治疗提供信息。我们使用了 17 年间(2000-2017 年)在法国收集的 912 株 BSI 和 370 株普通大肠杆菌分离物。我们比较了它们的泛基因组、遗传背景(系统群、ST、O 群)、毒力相关基因(VAG)和抗菌药耐药性基因的存在情况,发现在所有比较中,共生菌和 BSI 分离物之间都存在显著差异。以来自泛基因组的所有遗传变异为基础并控制种群结构的机器学习线性模型揭示了 VAG 的类似差异,发现了与致病性(引起 BSI 的能力)相关的新变异,并准确地将 BSI 菌株与普通菌株进行了分类。致病性是一种高遗传性状,细菌基因变异可解释高达 69% 的变异。最后,通过对 1980 年的共生菌株进行补充,我们预测致病性在 1980 年、2000 年到 2010 年期间持续上升。我们的研究结果表明,大肠杆菌在共生和致病之间的转变过程中表现出了巨大的遗传变异,而且该物种正朝着更高的致病性演化。
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来源期刊
PLoS Genetics
PLoS Genetics 生物-遗传学
CiteScore
8.10
自引率
2.20%
发文量
438
审稿时长
1 months
期刊介绍: PLOS Genetics is run by an international Editorial Board, headed by the Editors-in-Chief, Greg Barsh (HudsonAlpha Institute of Biotechnology, and Stanford University School of Medicine) and Greg Copenhaver (The University of North Carolina at Chapel Hill). Articles published in PLOS Genetics are archived in PubMed Central and cited in PubMed.
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