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The Yersiniabactin-Associated ATP Binding Cassette Proteins YbtP and YbtQ Enhance Escherichia coli Fitness during High-Titer Cystitis

Infect Immun. 2016 Apr 22;84(5):1312-1319. doi: 10.1128/IAI.01211-15. Print 2016 May.

Abstract

The Yersinia high-pathogenicity island (HPI) is common to multiple virulence strategies used by Escherichia coli strains associated with urinary tract infection (UTI). Among the genes in this island are ybtP and ybtQ, encoding distinctive ATP binding cassette (ABC) proteins associated with iron(III)-yersiniabactin import in Yersinia pestis In this study, we compared the impact of ybtPQ on a model E. coli cystitis strain during in vitro culture and experimental murine infections. A ybtPQ-null mutant exhibited no growth defect under standard culture conditions, consistent with nonessentiality in this background. A growth defect phenotype was observed and genetically complemented in vitro during iron(III)-yersiniabactin-dependent growth. Following inoculation into the bladders of C3H/HEN and C3H/HeOuJ mice, this strain exhibited a profound, 10(6)-fold competitive infection defect in the subgroup of mice that progressed to high-titer bladder infections. These results identify a virulence role for YbtPQ in the highly inflammatory microenvironment characteristic of high-titer cystitis. The profound competitive defect may relate to the apparent selection of Yersinia HPI-positive E. coli in uncomplicated clinical UTIs.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cystitis / microbiology*
  • Cystitis / pathology
  • Disease Models, Animal
  • Escherichia coli / genetics
  • Escherichia coli / pathogenicity*
  • Female
  • Gene Deletion
  • Genetic Complementation Test
  • Mice, Inbred C3H
  • Phenols / metabolism*
  • Siderophores / metabolism
  • Thiazoles / metabolism*
  • Virulence Factors / genetics
  • Virulence Factors / metabolism*

Substances

  • ATP-Binding Cassette Transporters
  • Bacterial Proteins
  • Phenols
  • Siderophores
  • Thiazoles
  • Virulence Factors
  • YbtP protein, Yersinia pestis
  • YbtQ protein, Yersinia pestis
  • yersiniabactin