Surface proteins of Strep A
Group A Streptococcus (S. pyogenes or Strep A) remains a major public health threat. This widespread gram-positive bacterial pathogen causes acute invasive diseases and gives rise to severe autoimmune sequelae, and is responsible for morbidity and mortality on a global scale. An essential virulence factor of Strep A, the antigenically variable M protein, enables the bacterium to evade opsonophagocytic killing by the immune system. The M protein confers this indispensable function of phagocyte resistance by recruiting specific soluble human proteins to the GAS surface that block the deposition of the major opsonin C3b as well as antigen-specific opsonic antibodies. In some Strep A strains, an M-like protein serves this function. We are investigating the structural biology and biochemistry of interactions of M and M-like proteins with human targets, and testing functional hypotheses generated by our structural studies through microbiological and immunological experiments. X-ray crystallography has been the prime methodology applied to structural investigations, but others (e.g., EM, NMR, CD) have been applied to address specific questions. The ultimate goal of our studies, which are carried out in collaboration with Victor Nizet, is to provide essential guidance to designing anti-virulence and vaccination strategies against Strep A.