Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
Veterans Affairs Medical Center and University of Minnesota, Minneapolis, MN, USA.
Nat Commun. 2020 Nov 24;11(1):5968. doi: 10.1038/s41467-020-19714-9.
Escherichia coli is the leading cause of urinary tract infection, one of the most common bacterial infections in humans. Despite this, a genomic perspective is lacking regarding the phylogenetic distribution of isolates associated with different clinical syndromes. Here, we present a large-scale phylogenomic analysis of a spatiotemporally and clinically diverse set of 907 E. coli isolates, including 722 uropathogenic E. coli (UPEC) isolates. A genome-wide association approach identifies the (P-fimbriae-encoding) papGII locus as the key feature distinguishing invasive UPEC, defined as isolates associated with severe UTI, i.e., kidney infection (pyelonephritis) or urinary-source bacteremia, from non-invasive UPEC, defined as isolates associated with asymptomatic bacteriuria or bladder infection (cystitis). Within the E. coli population, distinct invasive UPEC lineages emerged through repeated horizontal acquisition of diverse papGII-containing pathogenicity islands. Our findings elucidate the molecular determinants of severe UTI and have implications for the early detection of this pathogen.
大肠杆菌是尿路感染的主要原因，是人类最常见的细菌感染之一。尽管如此，对于与不同临床综合征相关的分离株的系统发育分布，还缺乏基因组的观点。在这里，我们对一组具有时空和临床多样性的 907 株大肠杆菌分离株进行了大规模的系统基因组分析，其中包括 722 株尿路致病性大肠杆菌（UPEC）分离株。全基因组关联分析确定了（P-菌毛编码）papGII 基因座是区分侵袭性 UPEC 的关键特征，侵袭性 UPEC 定义为与严重尿路感染相关的分离株，即与肾感染（肾盂肾炎）或尿源菌血症相关的分离株，而非侵袭性 UPEC 定义为与无症状菌尿或膀胱感染（膀胱炎）相关的分离株。在大肠杆菌群体中，通过反复横向获得不同含有 papGII 的致病性岛，出现了不同的侵袭性 UPEC 谱系。我们的研究结果阐明了严重尿路感染的分子决定因素，并对该病原体的早期检测具有重要意义。
