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

Published

Journal Article

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.

Full Text

Cited Authors

  • Hannan, TJ; Mysorekar, IU; Chen, SL; Walker, JN; Jones, JM; Pinkner, JS; Hultgren, SJ; Seed, PC

Published Date

  • January 2008

Published In

Volume / Issue

  • 67 / 1

Start / End Page

  • 116 - 128

PubMed ID

  • 18036139

Pubmed Central ID

  • 18036139

International Standard Serial Number (ISSN)

  • 0950-382X

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2958.2007.06025.x

Language

  • eng

Conference Location

  • England