Rare emergence of symptoms during long-term asymptomatic Escherichia coli 83972 carriage without an altered virulence factor repertoire

J Urol. 2014 Feb;191(2):519-28. doi: 10.1016/j.juro.2013.07.060. Epub 2013 Jul 30.

Abstract

Purpose: Asymptomatic bacteriuria established by intravesical inoculation of Escherichia coli 83972 is protective in patients with recurrent urinary tract infections. In this randomized, controlled crossover study a total of 3 symptomatic urinary tract infection episodes developed in 2 patients while they carried E. coli 83972. We examined whether virulence reacquisition by symptom isolates may account for the switch from asymptomatic bacteriuria to symptomatic urinary tract infection.

Materials and methods: We used E. coli 83972 re-isolates from 2 patients in a prospective study and from another 2 in whom symptoms developed after study completion. We phylogenetically classified the re-isolates, and identified the genomic restriction patterns and gene expression profiles as well as virulence gene structure and phenotypes. In vivo virulence was examined in the murine urinary tract infection model.

Results: The fim, pap, foc, hlyA, fyuA, iuc, iroN, kpsMT K5 and malX genotypes of the symptomatic re-isolates remained unchanged. Bacterial gene expression profiles of flagellated symptomatic re-isolates were unique to each host, providing no evidence of common deregulation. Symptomatic isolates did not differ in virulence from the wild-type strain, as defined in the murine urinary tract infection model by persistence, symptoms or innate immune activation.

Conclusions: The switch from asymptomatic E. coli 83972 carriage to symptomatic urinary tract infection was not explained by reversion to a functional virulence gene repertoire.

Keywords: ABU; Escherichia coli; IFNγ; IL; K5 capsule; LPS; PMN; UTI; aerobactin; asymptomatic bacteriuria; cnf1; cytotoxic-necrotizing factor1; fyuA; gene expression; hlyA; interferon-γ; interleukin; iroN; iuc; kpsMT K5; lipopolysaccharide; polymorphonuclear leukocyte; salmochelin receptor; urinary bladder; urinary tract infection; urinary tract infections; virulence; wild type; wt; yersiniabactin receptor; α-hemolysin.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Asymptomatic Infections*
  • Carrier State / microbiology
  • Cross-Over Studies
  • Disease Models, Animal
  • Escherichia coli / genetics*
  • Escherichia coli / isolation & purification
  • Escherichia coli / pathogenicity*
  • Escherichia coli Infections / microbiology*
  • Female
  • Gene Expression Profiling
  • Humans
  • Male
  • Mice
  • Microbial Sensitivity Tests
  • Middle Aged
  • Phenotype
  • Prospective Studies
  • Recurrence
  • Urinary Tract Infections / genetics*
  • Urinary Tract Infections / microbiology
  • Virulence / genetics