The IrgA homologue adhesin Iha is an Escherichia coli virulence factor in murine urinary tract infection.
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.
Johnson
James R
JR
Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, Campus Box 8208, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Jelacic
Srdjan
S
Schoening
Laura M
LM
Clabots
Connie
C
Shaikh
Nurmohammad
N
Mobley
Harry L T
HL
Tarr
Phillip I
PI
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
D018830:Adhesins, Escherichia coli