Immunomodulating Enzymes from Streptococcus pyogenes-In Pathogenesis, as Biotechnological Tools, and as Biological Drugs

Streptococcus pyogenes, or Group A Streptococcus, is an exclusively human pathogen that causes a wide variety of diseases ranging from mild throat and skin infections to severe invasive disease. The pathogenesis of S. pyogenes infection has been extensively studied, but the pathophysiology, especially of the more severe infections, is still somewhat elusive. One key feature of S. pyogenes is the expression of secreted, surface-associated, and intracellular enzymes that directly or indirectly affect both the innate and adaptive host immune systems. Undoubtedly, S. pyogenes is one of the major bacterial sources for immunomodulating enzymes. Major targets for these enzymes are immunoglobulins that are destroyed or modified through proteolysis or glycan hydrolysis. Furthermore, several enzymes degrade components of the complement system and a group of DNAses degrade host DNA in neutrophil extracellular traps. Additional types of enzymes interfere with cellular inflammatory and innate immunity responses. In this review, we attempt to give a broad overview of the functions of these enzymes and their roles in pathogenesis. For those enzymes where experimentally determined structures exist, the structural aspects of the enzymatic activity are further discussed. Lastly, we also discuss the emerging use of some of the enzymes as biotechnological tools as well as biological drugs and vaccines.