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Mechanical manipulation of the epithelial cytoskeleton by type IV pili

Enno Oldewurtel

With many bacteria that cause human diseases, pilus-mediated adhesion to their host mammalian cells is the first step towards infection. Bacterial adhesion often triggers the rearrangement of the host cytoskeleton. Bacteria can hitchhike natural mammalian signalling pathways to prepare the host cytoskeleton for phagocytosis. In particular, pilus-mediated adhesion of microcolonies induces plaque formation in epithelial cells, in which transmembrane receptors, ezrin, actin and other proteins accumulate locally at the site of bacterial adhesion.

With many bacteria that cause human diseases, pilus-mediated adhesion to their host mammalian cells is the first step towards infection. Bacterial adhesion often triggers the rearrangement of the host cytoskeleton. Bacteria can hitchhike natural mammalian signalling pathways to prepare the host cytoskeleton for phagocytosis. In particular, pilus-mediated adhesion of microcolonies induces plaque formation in epithelial cells, in which transmembrane receptors, ezrin, actin and other proteins accumulate locally at the site of bacterial adhesion

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Model for uptake of epithelial cells of Neisseriae

Various mammalian cell types can sense and generate mechanical forces on the order of 10pN to 10nN. We have shown recently with isolated gonococci, that single type IV pili generate very high molecular force in the range of 100pN. During infection with bacterial mutants that generate pili but are inhibited in force generation, plaque formation is strongly reduced. The goal of this project is to better understand the role of mechanical force generated by type IV pili on the local dynamics and remodelling of the cytoskeleton in epithelial host cells.

Techniques

  • Laser Tweezer
  • FRAP (Fluorescence Recovery after Photobleaching)
  • Quantitaive Image Analysis

Publications

  • Opitz, D., Maier, B. Rapid cytoskeletal response ot epithelial cells to force generation by type IV pili. PLoS One 6(2), e17088 (2011)
  • Opitz, D., Clausen, M., Maier, B. Dynamics of gonococcal type IV pili during infection. ChemPhysChem 10(9) (2009)