Poster Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Caveolin-1 restricts group A Streptococcus invasion into non-phagocytic host cells (#187)

Timothy Barnett 1 2 , Jin Yan Lim 1 , Michele Bastiani 3 , Kerrie-Ann McMahon 3 , Charles Ferguson 3 , Richard Webb 4 , Robert Parton 3 , Mark Walker 1
  1. Australian Infectious Diseases Research Centre, University of Queensland, St Lucia, QLD, Australia
  2. Telethon Kids Institute, Subiaco, WA, Australia
  3. Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD, Australia
  4. Centre for Microscopy and Microanalysis, University of Queensland, St Lucia, QLD, Australia

Caveolae are composed of two major proteins, caveolin-1 (CAV1) and cavin-1/polymerase transcript factor I (CAVIN1). Here we demonstrate that CAV1 levels modulate invasion of group A Streptococcus (GAS) into non-phagocytic mammalian cells. GAS showed enhanced internalization into CAV1 knockout mouse embryonic fibroblasts (MEFs), and CAV1 knockdown human epithelial HEp-2 cells, whereas over-expression of CAV1 in HEp-2 cells reduced GAS invasion. This effect was not dependent on the expression of the GAS fibronectin binding protein SfbI, which had previously been implicated in caveolae-mediated uptake. Nor was this effect dependent on CAVIN1, as knockout of CAVIN1 in MEFs resulted in reduced GAS internalization. While CAV1 restricted GAS invasion into host cells, we observed only minimal association of invading GAS (strain M1T15448) with CAV1 by immunofluorescence, and very low association of invading M1T15448 with caveolae by transmission electron microscopy. These observations suggest that physical interaction with caveolae is not needed for CAV1 restriction of invading GAS. An indirect mechanism of action is also consistent with the finding that changing membrane fluidity reverses the increased invasion observed in CAV1-null cells. Together, these results suggest that CAV1 protects host cells against GAS invasion by a caveolae-independent mechanism.