title: Strain-specific impact of the high-pathogenicity island on virulence in extra-intestinal pathogenic Escherichia coli.
abstract: In order to clarify the role of the high-pathogenicity island (HPI) in the experimental virulence of Escherichia coli, we constructed different deletion mutants of the entire HPI and of three individual genes (irp2, fyuA and ybtA), encoding for three main functions within the HPI. Those mutants were constructed for three phylogroup B2 strains (536-STc127, CFT073-STc73, and NU14-STc95), representative of the main B2 subgroups causing extra-intestinal infections. Transcriptional profiles obtained for the selected HPI genes irp2, fyuA and ybtA revealed similar patterns for all strains, both under selective iron-deplete conditions and in intracellular bacterial communities in vitro, with a high expression of irp2. Deletion of irp2 and ybtA abrogated yersiniabactin production, whereas the fyuA knockout was only slightly impaired for siderophore synthesis. The experimental virulence of the strains was then tested in amoeba Dictyostelium discoideum and mouse septicaemia models. No effect of any HPI mutant was observed for the two more virulent strains 536 and CFT073. In contrast, the virulence of the less virulent NU14 strain was dramatically diminished by the complete deletion of the HPI and irp2 gene whereas a lesser reduction in virulence was observed for the fyuA and ybtA deletion mutants. The two experimental virulence models gave similar results. It appears that the role of the HPI in experimental virulence is depending on the genetic background of the strains despite similar inter-strain transcriptional patterns of HPI genes, as well as of the functional class of the studied gene. Altogether, these data indicate that the intrinsic extra-intestinal virulence in the E. coli species is multigenic, with epistatic interactions between the genes.
authors.affiliation: INSERM, IAME, UMR1137, Paris, France; Univ Paris Nord, IAME, UMR1137, Sorbonne Paris Cité, Bobigny, France; APHP, Hôpitaux Universitaires Paris Seine Saint-Denis, Site Avicenne, Bobigny, France.
authors.forename: Mounira
authors.initials: M
authors.lastname: Smati
authors.affiliation: Department of Urology, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Magistro
authors.affiliation: Institut de Biologie de l'Ecole Normale Supérieure, ENS, CNRS UMR8197, INSERM U1024, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Adiba
authors.affiliation: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, München, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wieser
authors.affiliation: INSERM, IAME, UMR1137, Paris, France; Univ Paris Nord, IAME, UMR1137, Sorbonne Paris Cité, Bobigny, France; APHP, Hôpitaux Universitaires Paris Seine Saint-Denis, Site Avicenne, Bobigny, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Picard
authors.affiliation: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, München, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Schubert
authors.affiliation: INSERM, IAME, UMR1137, Paris, France; Univ Paris Diderot, IAME, UMR1137, Sorbonne Paris Cité, Paris, France; APHP, Hôpitaux Universitaires Paris Nord Val de Seine Saint-Denis, Paris, France. Electronic address: erick.denamur@inserm.fr.
authors.forename: Erick
authors.initials: E
authors.lastname: Denamur
mesh_terms: D000818:Animals; D002470:Cell Survival; D004023:Dictyostelium / Q000382:microbiology / Q000502:physiology; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development*; D004927:Escherichia coli Infections / Q000453:epidemiology / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D044404:Genomic Islands; D051379:Mice; D018805:Sepsis / Q000453:epidemiology / Q000473:pathology; D014774:Virulence
keywords: Escherichia coli; Experimental virulence; Genetic background; High pathogenicity island