Lim, Jin Yan, Barnett, Timothy C., Bastiani, Michele, McMahon, Kerrie-Ann, Ferguson, Charles, Webb, Richard I., Parton, Robert G., and Walker, Mark J. (2017) Caveolin 1 restricts Group A Streptococcus invasion of nonphagocytic host cells. Cellular Microbiology, 19 (12). e12772.

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Abstract

Caveolae are composed of 2 major proteins, caveolin 1 (CAV1) and cavin 1 or polymerase tran-script release factor I (CAVIN1). Here, we demonstrate that CAV1 levels modulate invasion ofGroup AStreptococcus(GAS) into nonphagocytic mammalian cells. GAS showed enhancedinternalisation into CAV1‐knockout mouse embryonic fibroblasts and CAV1 knockdown humanepithelial HEp‐2 cells, whereas overexpression 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 depen-dent on CAVIN1, as knockout of CAVIN1 in mouse embryonic fibroblasts resulted in reducedGAS internalisation. Although CAV1 restricted GAS invasion into host cells, we observed onlyminimal association of invading GAS (strain M1T15448) with CAV1 by immunofluorescence andvery low association of invading M1T15448with caveolae by transmission electron microscopy.These observations suggest that physical interaction with caveolae is not needed for CAV1restriction of invading GAS. An indirect mechanism of action is also consistent with the findingthat 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 cave-ola‐independent mechanism.

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