Contribution of Streptococcal Collagen-Like Protein (Scl-1) in the Resistance to Phagocytic Killing of Group A Streptococcus
Authors:Sabina Anik, Simon Doehrmann, Neelou Etesami, Victor Nizet
Mentor:Cheryl Okumura, Assistant Professor of Biology, Biology Department, Occidental College, Department of Pediatrics, University of California, San Diego
Group A Streptococcus is a globally disseminated pathogen capable of causing a wide spectrum of diseases. Invasive GAS strains have been characterized by a variety of up-regulated genes resulting from a genomic mutation in the covR/S regulatory region, some of which have been identified as virulence factors. The up-regulation of the gene encoding streptococcal collagen-like protein (scl-1), a surface protein in the M1 serotype, has been hypothesized to promote bacterial resistance to host defenses. When incubated with phagocytic cells, an scl-1 mutant strain demonstrates significantly decreased survival compared with wild-type and plasmid-complemented strains. The current study aims to determine the molecular mechanism by which Scl-1 contributes to bacterial survival. Our data shows that Scl-1 contributes to resistance to reactive oxygen species (ROS) such as peroxide and hypochloric acid, despite GAS being a catalase-negative strain. However, preliminary data indicates no difference in peroxide production by phagocytic cells in response to incubation with the different Scl-1 strains. These results suggest that Scl-1 provides direct resistance to oxidative burst-mediated killing. Additionally, Scl-1 contributed to resistance to the antimicrobial peptide cathelicidin (LL-37). Preliminary data using lysozyme treatments to lyse the bacterial cell walls show that the scl-1 mutant strain was more susceptible to killing by lysozyme. Altogether, these data suggest that the surface protein Scl-1 serves as a physical barrier to protect the bacteria from antimicrobial molecules produced by phagocytic cells. Our work continues to elucidate the molecular mechanisms behind the virulence of GAS and contributes to the search for novel therapies and vaccines aimed at treating and preventing GAS infection.