Host cell caveolae act as an entry-port for group A streptococci

Area of Science:

• Microbiology
• Cell Biology
• Infectious Diseases

Background:

• Group A Streptococcus (GAS) is a significant human pathogen.
• Understanding bacterial invasion mechanisms is crucial for developing targeted therapies.

Purpose of the Study:

• To elucidate the entry mechanism of Group A Streptococcus into host cells.
• To identify the role of host cell structures and bacterial factors in invasion.

Main Methods:

• Scanning electron microscopy and ultrathin sectioning of infected epithelial and endothelial cells.
• Immunofluorescence staining for caveolin-1 and endosomal/lysosomal markers.
• Disruption of caveolae using methyl-beta-cyclodextrin and filipin.
• Functional assays using non-invasive Streptococcus gordonii expressing SfbI and purified SfbI protein.

Main Results:

• Caveolae were identified as entry points for GAS, forming omega-shaped invaginations.
• Intracellular compartments, termed caveosomes, surrounded internalized streptococci and lacked endosomal markers.
• Disruption of caveolae inhibited bacterial invasion, and streptococci within caveosomes avoided lysosomal fusion.
• The streptococcal surface protein SfbI was identified as the key factor triggering caveolae-mediated invasion.

Conclusions:

• Group A Streptococcus utilizes host cell caveolae for entry into epithelial and endothelial cells.
• The streptococcal invasin SfbI protein activates a caveolae-mediated endocytic pathway, facilitating invasion and immune evasion.