Type 1 pilus-mediated bacterial invasion of bladder epithelial cells

Juan J. Martinez, Matthew A. Mulvey, Joel D. Schilling, Jerome S. Pinkner, Scott J. Hultgren

Research output: Contribution to journalArticlepeer-review

531 Scopus citations

Abstract

Most strains of uropathogenic Escherichia coli (UPEC) encode filamentous adhesive organelles called type 1 pili. We have determined that the type 1 pilus adhesin, FimH, mediates not only bacterial adherence, but also invasion of human bladder epithelial cells. In contrast, adherence mediated by another pilus adhesin, PapG, did not initiate bacterial internalization. FimH-mediated invasion required localized host actin reorganization, phosphoinositide 3-kinase (PI 3-kinase) activation and host protein tyrosine phosphorylation, but not activation of Src-family tyrosine kinases. Phosphorylation of focal adhesin kinase (FAK) at Tyr397 and the formation of complexes between FAK and PI 3-kinase and between α-actinin and vinculin were found to correlate with type 1 pilus-mediated bacterial invasion. Inhibitors that prevented bacterial invasion also blocked the formation of these complexes. Our results demonstrate that UPEC strains are not strictly extracellular pathogens and that the type 1 pilus adhesin FimH can directly trigger host cell signaling cascades that lead to bacterial internalization.

Original languageEnglish
Pages (from-to)2803-2812
Number of pages10
JournalEMBO Journal
Volume19
Issue number12
DOIs
StatePublished - Jun 15 2000

Keywords

  • Adhesin
  • Bladder
  • Invasion
  • Type 1 pili
  • Urinary tract infection

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