Oral Presentation BacPath 13: Molecular Analysis of Bacterial Pathogens Conference 2015

The role of caveolin-1 in the uptake of Streptococcus pyogenes into non-phagocytic host cells (#12)

Jin Yan Lim 1 2 , Timothy Barnett 1 2 , Kerrie-Ann McMahon 3 , Charles Ferguson 3 , Robert Parton 3 , Mark Walker 1 2
  1. Australian Infectious Diseases Research Centre, University of Queensland, St Lucia, QLD, Australia
  2. School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD, Australia
  3. Institute of Molecular Biosciences, University of Queensland, St Lucia, QLD, Australia

Streptococcus pyogenes, commonly known as Group A Streptococcus (GAS), is an obligate human pathogen that causes a wide array of diseases ranging from mild superficial infections to severe invasive diseases. It has previously been suggested that GAS invade human cells via host caveolae, which are pits found in cell plasma membranes that are involved in a wide variety of cellular processes. While prior studies demonstrated that GAS co-localized with host caveolae and that the disruption of caveolae with chemical inhibitors lead to reduced intracellular GAS, the underlying molecular mechanism of this process was not elucidated. To confirm the role of caveolae during GAS invasion into non-phagocytic host cells, we first generated a stable knock down of caveolin-1 (CAV1), the major building block of caveolae, in human epithelial HEp-2 cells. To our surprise, we found increased GAS invasion into CAV1 knockdown cells, suggesting that CAV1 may protect against GAS invasion. Supporting this hypothesis, we found that over expression of CAV1 in wild type cells also resulted in decreased GAS invasion. While CAV1 levels clearly influence GAS invasion rates, we observed no co-localization of GAS with CAV1 by immunofluorescence, nor caveolae by electron microscopy, indicating that caveolae do not directly interact with GAS. Together, these results suggest that CAV1 protects host cells against GAS invasion and that it may serve as part of a novel innate immune defence mechanism against GAS invasion, that can be exploited to control infection.