title: The conserved nhaAR operon is drastically divergent between B2 and non-B2 Escherichia coli and is involved in extra-intestinal virulence.
abstract: The Escherichia coli species is divided in phylogenetic groups that differ in their virulence and commensal distribution. Strains belonging to the B2 group are involved in extra-intestinal pathologies but also appear to be more prevalent as commensals among human occidental populations. To investigate the genetic specificities of B2 sub-group, we used 128 sequenced genomes and identified genes of the core genome that showed marked difference between B2 and non-B2 genomes. We focused on the gene and its surrounding region with the strongest divergence between B2 and non-B2, the antiporter gene nhaA. This gene is part of the nhaAR operon, which is in the core genome but flanked by mobile regions, and is involved in growth at high pH and high sodium concentrations. Consistently, we found that a panel of non-B2 strains grew faster than B2 at high pH and high sodium concentrations. However, we could not identify differences in expression of the nhaAR operon using fluorescence reporter plasmids. Furthermore, the operon deletion had no differential impact between B2 and non-B2 strains, and did not result in a fitness modification in a murine model of gut colonization. Nevertheless, sequence analysis and experiments in a murine model of septicemia revealed that recombination in nhaA among B2 strains was observed in strains with low virulence. Finally, nhaA and nhaAR operon deletions drastically decreased virulence in one B2 strain. This effect of nhaAR deletion appeared to be stronger than deletion of all pathogenicity islands. Thus, a population genetic approach allowed us to identify an operon in the core genome without strong effect in commensalism but with an important role in extra-intestinal virulence, a landmark of the B2 strains.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) 1137, Paris, France; Laboratoire de Microbiologie, Hôpital Jean Verdier, Assistance Publique-Hôpitaux de Paris, Bondy, France et Université Paris Nord, Sorbonne Paris Cité, Paris, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Lescat
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) 1137, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Reibel
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) 1137, Paris, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Pintard
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) 1137, Paris, France; UMR 1137, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Dion
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) 1137, Paris, France; UMR 1137, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Glodt
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) 1137, Paris, France.
authors.forename: Cecile
authors.initials: C
authors.lastname: Gateau
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) 1137, Paris, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Launay
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) 1137, Paris, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Ledda
authors.forename: Stephane
authors.initials: S
authors.lastname: Cruveiller
authors.affiliation: Laboratoire de Génomique Comparative, Centre national de la Recherche Scientifique (CNRS) UMR 8030, Institut de Génomique, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Genoscope, Evry, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Cruvellier
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) 1137, Paris, France; Département d'Urologie, Néphrologie et Transplantation, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris et Université Pierre et Marie Curie, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Tourret
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) 1137, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tenaillon
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000254:growth & development / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D005260:Female; D016680:Genome, Bacterial; D006863:Hydrogen-Ion Concentration; D051379:Mice; D009876:Operon; D009994:Osmolar Concentration; D010641:Phenotype; D010802:Phylogeny; D018805:Sepsis / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D017923:Sodium-Hydrogen Exchangers / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate; D014157:Transcription Factors / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D014774:Virulence
chemical_list: D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C102839:NhaA protein, E coli; D017923:Sodium-Hydrogen Exchangers; D014157:Transcription Factors; C074687:nhaR protein, E coli