RT Journal Article SR Electronic T1 Major role of the high-pathogenicity island (HPI) in the intrinsic extra-intestinal virulence of Escherichia coli revealed by a genome-wide association study JF bioRxiv FD Cold Spring Harbor Laboratory SP 712034 DO 10.1101/712034 A1 Marco Galardini A1 Olivier Clermont A1 Alexandra Baron A1 Bede Busby A1 Sara Dion A1 Sören Schubert A1 Pedro Beltrao A1 Erick Denamur YR 2019 UL http://biorxiv.org/content/early/2019/07/23/712034.abstract AB The bacterium Escherichia coli is not only an important gut commensal, but also a common pathogen involved in both diarrheic and extra-intestinal diseases. To characterize the genetic determinants of extra-intestinal virulence we carried out an unbiased genome-wide association study (GWAS) on 234 commensal and extra-intestinal pathogenic strains representative of the species phylogenetic diversity, tested in a mouse model of sepsis. We found that the high-pathogenicity island (HPI), a ~35 kbp gene island encoding the yersiniabactin siderophore, is highly associated with death in mice, surpassing all other genetic factors by far. We validated the association in vivo by deleting key components of the HPI in strains in two phylogenetic backgrounds, and found that virulence is correlated with growth in the presence of various compounds including several antimicrobials, which hints at collateral sensitivities associated with intrinsic pathogenicity. This study points at the power of unbiased genetic approaches to uncover virulence determinants and the use of phenotypic data to generate new hypothesis on pathogenicity and phenotypic characteristics associated with it.