Caveolin 1 restricts Group A Streptococcus invasion of nonphagocytic host cells

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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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.

Item ID: 75604
Item Type: Article (Research - C1)
ISSN: 1462-5822
Copyright Information: © 2017 John Wiley & Sons Ltd
Funders: Australian Research Council (ARC)
Projects and Grants: ARC APP1037320, ARC APP1041294, ARC APP1045092, ARC APP1058565, ARC APP1071659, ARC APP1102621, ARC APP569542, ARC CE140100036, ARC DE140100558
Date Deposited: 03 Aug 2022 00:42
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320701 Medical bacteriology @ 20%
31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310799 Microbiology not elsewhere classified @ 70%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3299 Other biomedical and clinical sciences > 329999 Other biomedical and clinical sciences not elsewhere classified @ 10%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 100%
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