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，尿路感染是人类最常见的细菌感染之一。尽管如此，关于与不同临床综合征相关的分离株的系统发育分布，仍缺乏基因组视角。在这里，我们对 907 株大肠杆菌分离株（包括 722 株尿路致病性大肠杆菌(UPEC) 分离株）进行了大规模系统发育分析。全基因组关联方法将（P-菌毛编码） papGII位点识别为区分侵袭性 UPEC 的关键特征，UPEC 定义为与严重 UTI（即肾脏感染（肾盂肾炎）或尿源性菌血症）相关的分离株与非侵袭性 UPEC 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，通过重复水平获取不同的含有papGII的致病性岛，出现了独特的侵入性 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，并对这种病原体的早期检测具有重要意义。