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LeuX tRNA‐dependent and ‐independent mechanisms of Escherichia coli pathogenesis in acute cystitis
Author(s) -
Hannan Thomas J.,
Mysorekar Indira U.,
Chen Swaine L.,
Walker Jennifer N.,
Jones Jennifer M.,
Pinkner Jerome S.,
Hultgren Scott J.,
Seed Patrick C.
Publication year - 2008
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2007.06025.x
Subject(s) - biology , pilus , virulence , pathogenesis , recombinase , escherichia coli , microbiology and biotechnology , gene , phase variation , locus (genetics) , genetics , immunology , recombination
Summary 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.