PilT is required for PI(3,4,5)P3-mediated crosstalk between Neisseria gonorrhoeae and epithelial cells

Shaun W. Lee, Dustin L. Higashi, Aurelie Snyder, Alexey J. Merz, Laura Potter, Magdalene So

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

The retractile type IV pilus participates in a number of fundamental bacterial processes, including motility, DNA transformation, fruiting body formation and attachment to host cells. Retraction of the N. gonorrhoeae type IV pilus requires a functional pilT. Retraction generates substantial force on its substrate (> 100 pN per retraction event), and it has been speculated that epithelial cells sense and respond to these forces during infection. We provide evidence that pillated, Opa non-expressing Neisseria gonorrhoeae activates the stress-responsive PI-3 kinase/Akt (PKB) pathway in human epithelial cells, and activation is enhanced by a functional pilT. PI-3 kinase inhibitors wortmannin and LY294002 reduce cell entry by 81% and 50%, respectively, illustrating the importance of this cascade in bacterial invasion. PI-3 kinase and its direct downstream effectors [PI(3,4,5)P3] and Akt are concentrated in the cell cortex beneath adherent bacteria, particularly at the periphery of the bacterial microcolonies. Furthermore, [PI(3,4,5)P3] is translocated to the outer leaflet of the plasma membrane. Finally, we show that [PI(3,4,5)P3] stimulates microcolony formation and upregulates pilT expression in vitro. We conclude that N. gonorrhoeae activation of PI-3 kinase triggers the host cell to produce a lipid second messenger that influences bacterial behaviour.

Original languageEnglish (US)
Pages (from-to)1271-1284
Number of pages14
JournalCellular Microbiology
Volume7
Issue number9
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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