Escherichia coli 83972 expressing a P fimbriae oligosaccharide receptor mimic impairs adhesion of uropathogenic E. coli

J Infect Dis. 2012 Oct;206(8):1242-9. doi: 10.1093/infdis/jis493. Epub 2012 Aug 7.

Abstract

Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are a significant health concern, exacerbated by the rapid emergence of multidrug resistant strains refractory to antibiotic treatment. P fimbriae are strongly associated with upper urinary tract colonization due to specific binding to α-D-galactopyranosyl-(1-4)-β-D-galactopyranoside receptors in the kidneys. Thus, inhibiting P-fimbrial adhesion may reduce the incidence of UPEC-mediated UTI. E. coli 83972 is an asymptomatic bacteriuria isolate successfully used as a prophylactic agent to prevent UTI in human studies. We constructed a recombinant E. coli 83972 strain displaying a surface-located oligosaccharide P fimbriae receptor mimic that bound to P-fimbriated E. coli producing any of the 3 PapG adhesin variants. The recombinant strain, E. coli 83972::lgtCE, impaired P fimbriae-mediated adhesion to human erythrocytes and kidney epithelial cells. Additionally, E. coli 83972::lgtCE impaired urine colonization by UPEC in a mouse UTI model, demonstrating its potential as a prophylactic agent to prevent UTI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Adhesion*
  • Disease Models, Animal
  • Epithelial Cells / microbiology
  • Erythrocytes / microbiology
  • Female
  • Fimbriae Proteins / genetics
  • Fimbriae Proteins / metabolism*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Oligosaccharides / genetics
  • Oligosaccharides / metabolism*
  • Protein Binding
  • Urinary Tract Infections / prevention & control
  • Uropathogenic Escherichia coli / genetics
  • Uropathogenic Escherichia coli / pathogenicity*

Substances

  • Oligosaccharides
  • Fimbriae Proteins