Université Paris Cité, IAME, INSERM, Paris, France.
Département de Prévention, Diagnostic et Traitement des Infections, Hôpital Henri Mondor, Créteil, France.
Nat Commun. 2023 Jun 20;14(1):3667. doi: 10.1038/s41467-023-39428-y.
The intrinsic virulence of extra-intestinal pathogenic Escherichia coli is associated with numerous chromosomal and/or plasmid-borne genes, encoding diverse functions such as adhesins, toxins, and iron capture systems. However, the respective contribution to virulence of those genes seems to depend on the genetic background and is poorly understood. Here, we analyze genomes of 232 strains of sequence type complex STc58 and show that virulence (quantified in a mouse model of sepsis) emerged in a sub-group of STc58 due to the presence of the siderophore-encoding high-pathogenicity island (HPI). When extending our genome-wide association study to 370 Escherichia strains, we show that full virulence is associated with the presence of the aer or sit operons, in addition to the HPI. The prevalence of these operons, their co-occurrence and their genomic location depend on strain phylogeny. Thus, selection of lineage-dependent specific associations of virulence-associated genes argues for strong epistatic interactions shaping the emergence of virulence in E. coli.
肠外致病性大肠杆菌的固有毒力与许多染色体和/或质粒携带的基因有关，这些基因编码多种功能，如黏附素、毒素和铁捕获系统。然而，这些基因对毒力的各自贡献似乎取决于遗传背景，目前了解甚少。在这里，我们分析了 232 株序列型复合物 STc58 的基因组，结果表明，由于存在铁载体编码的高致病性岛（HPI），STc58 的一个亚群中出现了毒力（在败血症的小鼠模型中进行定量）。当我们将全基因组关联研究扩展到 370 株大肠杆菌时，我们发现除了 HPI 之外，完整的毒力还与 aer 或 sit 操纵子的存在有关。这些操纵子的流行程度、它们的共存和它们的基因组位置取决于菌株的系统发育。因此，与毒力相关基因的特定关联的选择表明存在强烈的上位性相互作用，这些相互作用塑造了大肠杆菌毒力的出现。
