Electronic Thesis and Dissertation Repository

Role of the fibronectin-binding, collagen-binding, T-antigen region during nasopharyngeal infection by Streptococcus pyogenes

Akshay Sule, The University of Western Ontario

Abstract

Streptococcus pyogenes is a human-specific pathogen that uses a variety of adhesion molecules in order to initiate pharyngeal infection and maintain colonization. One genomic locus that is believed to contribute to adherence is the fibronectin-binding, collagen-binding, T-antigen (FCT) region, primarily due to the inclusion of genes that encode for a pilus (tee18.1), collagen-binding protein (cpa), and fibronectin-binding protein (prtF2). The precise role of these genes and the FCT region as a whole, however, have yet to be elucidated within the context of pharyngeal infection. In this study, we utilize the M18 serotype S. pyogenes strain MGAS8232 to demonstrate that the presence of the FCT region is critical in binding collagen type IV and fibronectin, and is additionally required for invasion into human pharyngeal cells, despite not impacting adherence to these cells. Furthermore, using a murine nasopharyngeal infection model, we determine that only cpa is expressed in vivo, and that removal of the FCT region does not impede the bacteria’s ability to establish infection. Overall, this study demonstrates that the FCT region is not involved during acute nasopharyngeal infection by S. pyogenes MGAS8232 but may contribute to the pathogenic life cycle through other mechanisms.