title: The IrgA homologue adhesin Iha is an Escherichia coli virulence factor in murine urinary tract infection.
abstract: The role of the Escherichia coli iron-regulated gene homologue adhesin (Iha) in the pathogenesis of urinary tract infections (UTIs) is unknown. We performed a series of complementary analyses to confirm or refute the hypothesis that Iha is a virulence factor in uropathogenic E. coli. Fecal E. coli isolates exhibited significantly lower prevalences of iha (range, 14 to 22%) than did clinical isolates from cases of pediatric cystitis or pyelonephritis, adult pyelonephritis or urosepsis, or bacteremia (range, 38 to 74%). Recombinant Iha from E. coli pyelonephritis isolate CFT073 conferred upon nonadherent E. coli ORN172 the ability to adhere to cultured T-24 human uroepithelial cells. In a well-established mouse model of ascending UTI, CFT073 and its derivative UPEC76 (a pap [P fimbriae] mutant version of strain CFT073) each significantly outcompeted their respective iha deletion mutants in CBA/J mice 48 h after bladder challenge (P < 0.03 for urine, both kidneys, and bladders of both constructs, except for bladders of mice challenged with UPEC76 and its deletion mutant, where P = 0.11). These data suggest that Iha(CFT073) is a virulence factor and might be a target for anti-UTI interventions.
authors.affiliation: Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, Campus Box 8208, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Johnson
authors.forename: Srdjan
authors.initials: S
authors.lastname: Jelacic
authors.forename: Laura M
authors.initials: LM
authors.lastname: Schoening
authors.forename: Connie
authors.initials: C
authors.lastname: Clabots
authors.forename: Nurmohammad
authors.initials: N
authors.lastname: Shaikh
authors.forename: Harry L T
authors.initials: HL
authors.lastname: Mobley
authors.forename: Phillip I
authors.initials: PI
authors.lastname: Tarr
mesh_terms: D018830:Adhesins, Escherichia coli / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D005260:Female; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D014552:Urinary Tract Infections / Q000276:immunology* / Q000378:metabolism
chemical_list: D018830:Adhesins, Escherichia coli