Epistatic interactions between the high pathogenicity island and other iron uptake systems shape Escherichia coli extra-intestinal virulence

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 associatedwith the presence of the aer or sit operons, in addition to the HPI. The prevalence of these operons, their cooccurrence 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.

Automated summary

The virulence of extra-intestinal pathogenic Escherichia coli is associated with various genes encoding adhesins, toxins, and iron capture systems, but the contribution of these genes to virulence depends on the genetic background and is not well understood. In this study, genome analysis of 232 strains reveals that the high-pathogenicity island (HPI), which encodes siderophores, is responsible for the emergence of virulence in a subgroup of strains. Furthermore, the presence of the aer or sit operons, in addition to the HPI, is associated with full virulence in E. coli, and their prevalence and genomic location depend on strain phylogeny. Overall, specific associations of virulence-associated genes indicate strong epistatic interactions shaping the emergence of virulence in E. coli.