LeuX tRNA-dependent and -independent mechanisms of Escherichia coli pathogenesis in acute cystitis.
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.
Hannan
Thomas J
TJ
Department of Molecular Microbiology and Microbial Pathogenesis, Washington University School of Medicine, St Louis, MO 63110, USA.
Mysorekar
Indira U
IU
Chen
Swaine L
SL
Walker
Jennifer N
JN
Jones
Jennifer M
JM
Pinkner
Jerome S
JS
Hultgren
Scott J
SJ
Seed
Patrick C
PC
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001483:Base Sequence; D003556:Cystitis / Q000382:microbiology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D036781:Fimbriae Proteins / Q000235:genetics / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D044404:Genomic Islands; D005839:Gentamicins / Q000494:pharmacology; D006384:Hemagglutination; D006801:Humans; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D012356:RNA, Transfer, Leu / Q000235:genetics / Q000378:metabolism*; D045522:Recombinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D001743:Urinary Bladder / Q000382:microbiology; D014552:Urinary Tract Infections / Q000382:microbiology; D019459:Urothelium / Q000382:microbiology; D014774:Virulence
D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D005839:Gentamicins; D012356:RNA, Transfer, Leu; D045522:Recombinases; D036781:Fimbriae Proteins; D019426:Integrases