The genus Escherichia is composed of several species and cryptic clades, including E. coli, which behaves as a vertebrate gut commensal, but also as an opportunistic pathogen involved in both diarrheic and extra-intestinal diseases. To characterize the genetic determinants of extra-intestinal virulence within the genus, we carried out an unbiased genome-wide association study (GWAS) on 370 commensal, pathogenic and environmental strains representative of the Escherichia genus phylogenetic diversity and including E. albertii (n = 7), E. fergusonii (n = 5), Escherichia clades (n = 32) and E. coli (n = 326), tested in a mouse model of sepsis. We found that the presence of the high-pathogenicity island (HPI), a ~35 kbp gene island encoding the yersiniabactin siderophore, is highly associated with death in mice, surpassing other associated genetic factors also related to iron uptake, such as the aerobactin and the sitABCD operons. We confirmed the association in vivo by deleting key genes of the HPI in E. coli strains in two phylogenetic backgrounds. We then searched for correlations between virulence, iron capture systems and in vitro growth in a subset of E. coli strains (N = 186) previously phenotyped across growth conditions, including antibiotics and other chemical and physical stressors. We found that virulence and iron capture systems are positively correlated with growth in the presence of numerous antibiotics, probably due to co-selection of virulence and resistance. We also found negative correlations between virulence, iron uptake systems and growth in the presence of specific antibiotics (i.e. cefsulodin and tobramycin), which hints at potential “collateral sensitivities” associated with intrinsic virulence. This study points to the major role of iron capture systems in the extra-intestinal virulence of the genus Escherichia.

属大肠杆菌是由几个物种和神秘的分支，其中包括ē。大肠杆菌，表现为脊椎动物的肠道共性，但也可能是与腹泻和肠外疾病有关的机会病原体。为了表征该属内肠道外毒力的遗传决定因素，我们对370株代表大肠杆菌属系统发生多样性并包括E的共生，致病和环境菌株进行了无偏基因组范围的关联研究（GWAS）。albertii（n = 7），E。弗格森氏菌（n = 5），大肠埃希氏菌（n = 32）和E。大肠杆菌（n = 326），在败血症的小鼠模型中进行了测试。我们发现高致病性岛（HPI）（约35 kbp的编码耶尔西菌素铁载体的基因岛）的存在与小鼠的死亡高度相关，超过了其他也与铁摄取有关的遗传因素，例如气杆菌素和该sitABCD操纵子。我们通过删除E中HPI的关键基因在体内证实了这种联系。在两个系统发育背景中的大肠杆菌菌株。然后，我们在E的子集中搜索毒力，铁捕获系统和体外生长之间的相关性。大肠杆菌以前在整个生长条件下表现型的菌株（N = 186），包括抗生素以及其他化学和物理应激源。我们发现，在多种抗生素存在下，毒力和铁捕获系统与生长呈正相关，这可能是由于毒力和耐药性的共同选择所致。我们还发现的毒力之间的负相关，铁摄取系统和生长在特定抗生素存在（我。Ë。头孢磺啶和妥布霉素），其在电势“附带敏感性”的提示与固有的毒力相关联。这项研究指出了铁捕获系统在埃希氏菌属的肠道外毒力中的主要作用。