LeuX tRNA-dependent and -independent mechanisms of Escherichia coli pathogenesis in acute cystitis

Mol Microbiol. 2008 Jan;67(1):116-28. doi: 10.1111/j.1365-2958.2007.06025.x. Epub 2007 Nov 25.


Uropathogenic Escherichia coli (UPEC) contain multiple horizontally acquired pathogenicity-associated islands (PAI) implicated in the pathogenesis of urinary tract infection. In a murine model of cystitis, type 1 pili-mediated bladder epithelial invasion and intracellular proliferation are key events associated with UPEC virulence. In this study, we examined the mechanisms by which a conserved PAI contributes to UPEC pathogenesis in acute cystitis. In the human UPEC strain UTI89, spontaneous excision of PAI II(UTI89) disrupts the adjacent leuX tRNA locus. Loss of wild-type leuX-encoded tRNA(5)(Leu) significantly delayed, but did not eliminate, FimB recombinase-mediated phase variation of type 1 pili. FimX, an additional FimB-like, leuX-independent recombinase, was also found to mediate type 1 pili phase variation. However, whereas FimX activity is relatively slow in vitro, it is rapid in vivo as a non-piliated strain lacking the other fim recombinases rapidly expressed type 1 pili upon experimental infection. Finally, we found that disruption of leuX, but not loss of PAI II(UTI89) genes, reduced bladder epithelial invasion and intracellular proliferation, independent of type 1 piliation. These findings indicate that the predominant mechanism for preservation of PAI II(UTI89) during the establishment of acute cystitis is maintenance of wild-type leuX, and not PAI II(UTI89) gene content.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Base Sequence
  • Cystitis / microbiology
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli / pathogenicity*
  • Escherichia coli Infections / microbiology*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Fimbriae Proteins / genetics
  • Fimbriae Proteins / metabolism
  • Fimbriae, Bacterial / metabolism
  • Gene Expression Regulation, Bacterial
  • Genomic Islands
  • Gentamicins / pharmacology
  • Hemagglutination
  • Humans
  • Integrases / genetics
  • Integrases / metabolism*
  • Mice
  • RNA, Transfer, Leu / genetics
  • RNA, Transfer, Leu / metabolism*
  • Recombinases / genetics
  • Recombinases / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Deletion
  • Urinary Bladder / microbiology
  • Urinary Tract Infections / microbiology
  • Urothelium / microbiology
  • Virulence


  • Anti-Bacterial Agents
  • Escherichia coli Proteins
  • Gentamicins
  • RNA, Transfer, Leu
  • Recombinases
  • Fimbriae Proteins
  • Integrases