he Contribution of Cell Envelope Proteinases to Immune Evasion Tactics of Group A Streptococcus

Abstract

Streptococcus pyogenes commonly known as Group A Streptococcus (GAS) represents one of the most lethal bacteria in humans with severe GAS disease affecting low-income countries disproportionately. Despite the heavy worldwide burden caused by GAS, a vaccine is yet to be commercially available. GAS causes a spectrum of disease with infections typically being mild but able to develop into acute conditions as post-infection immune sequelae or other invasive infections such as rheumatic heart disease or bacteraemia. GAS has evolved many ways to circumvent the various host immunogenic strategies with the neutrophil a key target. Although GAS produce proteins that aid in this process, Cell Envelope Proteinases (CEPs) play a vital role in degrading chemotactic gradients, establishing bacterial virulence, and protection against neutrophilic attacks. The key CEPs that GAS utilizes are the streptococcal C5a peptidase (ScpA) and S. pyogenes Cell Envelope Proteinase (SpyCEP) that degrade the complement anaphylatoxin C5a and the chemokine CXCL8, respectively. Degradation of these chemotactic gradients dampens the immune response and trumps neutrophil recruitment to the site of infection allowing infections to progress. Although these two CEPs belong to a much larger family of subtilisin-like proteases, their mechanisms of action are yet to be elucidated. In here, I review the contribution of CEPs to the immune consequences of GAS infections along with a proposed experimental plan to investigate the mechanism of CXCL8 cleavage by SpyCEP.