title: A role for the RNA chaperone Hfq in controlling adherent-invasive Escherichia coli colonization and virulence.
abstract: Adherent-invasive Escherichia coli (AIEC) has been linked with the onset and perpetuation of inflammatory bowel diseases. The AIEC strain LF82 was originally isolated from an ileal biopsy from a patient with Crohn's disease. The pathogenesis of LF82 results from its abnormal adherence to and subsequent invasion of the intestinal epithelium coupled with its ability to survive phagocytosis by macrophages once it has crossed the intestinal barrier. To gain further insight into AIEC pathogenesis we employed the nematode Caenorhabditis elegans as an in vivo infection model. We demonstrate that AIEC strain LF82 forms a persistent infection in C. elegans, thereby reducing the host lifespan significantly. This host killing phenotype was associated with massive bacterial colonization of the nematode intestine and damage to the intestinal epithelial surface. C. elegans killing was independent of known LF82 virulence determinants but was abolished by deletion of the LF82 hfq gene, which encodes an RNA chaperone involved in mediating posttranscriptional gene regulation by small non-coding RNAs. This finding reveals that important aspects of LF82 pathogenesis are controlled at the posttranscriptional level by riboregulation. The role of Hfq in LF82 virulence was independent of its function in regulating RpoS and RpoE activity. Further, LF82Δhfq mutants were non-motile, impaired in cell invasion and highly sensitive to various chemical stress conditions, reinforcing the multifaceted function of Hfq in mediating bacterial adaptation. This study highlights the usefulness of simple non-mammalian infection systems for the identification and analysis of bacterial virulence factors.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors.forename: Karina T
authors.initials: KT
authors.lastname: Simonsen
authors.forename: Gorm
authors.initials: G
authors.lastname: Nielsen
authors.forename: Janni Vester
authors.initials: JV
authors.lastname: Bjerrum
authors.forename: Thomas
authors.initials: T
authors.lastname: Kruse
authors.forename: Birgitte H
authors.initials: BH
authors.lastname: Kallipolitis
authors.forename: Jakob
authors.initials: J
authors.lastname: Møller-Jensen
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics; D017173:Caenorhabditis elegans / Q000382:microbiology; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000166:cytology / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000209:etiology*; D029968:Escherichia coli Proteins / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial; D035001:Host Factor 1 Protein / Q000502:physiology*; D007422:Intestines / Q000382:microbiology; D016601:RNA-Binding Proteins / Q000502:physiology; D014774:Virulence
chemical_list: D029968:Escherichia coli Proteins; C087373:Hfq protein, E coli; D035001:Host Factor 1 Protein; D016601:RNA-Binding Proteins