Immunomodulating Enzymes from Streptococcus pyogenes-In Pathogenesis, as Biotechnological Tools, and as Biological
Lotta Happonen1, Mattias Collin1
1Faculty of Medicine, Department of Clinical Sciences, Division of Infection Medicine, Lund University, SE-22184 Lund, Sweden.
Abstract:
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.
Insights
Streptococcus pyogenes, a common pathogen, uses various enzymes to evade host immunity, causing diverse infections. Understanding these bacterial enzymes is crucial for developing new treatments and biotechnological applications.
Area of Science:
- Microbiology
- Immunology
- Biochemistry
Background:
- Streptococcus pyogenes causes a spectrum of human diseases, from mild to severe invasive infections.
- The precise pathophysiology of severe S. pyogenes infections remains incompletely understood.
- Bacterial enzymes play a critical role in S. pyogenes pathogenesis by modulating host immune responses.
Purpose of the Study:
- To provide a comprehensive overview of Streptococcus pyogenes secreted and cell-associated enzymes.
- To elucidate the functions of these enzymes in host immune system modulation and pathogenesis.
- To discuss the structural basis of enzymatic activity and potential biotechnological applications.
Main Methods:
- Literature review of S. pyogenes pathogenesis and enzyme functions.
- Analysis of published data on enzyme targets, including immunoglobulins and complement components.
- Examination of structural data for key S. pyogenes enzymes.
Main Results:
- S. pyogenes expresses numerous enzymes that degrade host immune molecules like immunoglobulins and complement.
- Bacterial DNases degrade neutrophil extracellular traps, facilitating infection.
- Enzymes interfere with cellular inflammatory and innate immunity pathways.
Conclusions:
- Bacterial enzymes are key virulence factors for Streptococcus pyogenes, enabling immune evasion.
- Structural insights into these enzymes can inform therapeutic strategies.
- S. pyogenes enzymes hold potential as biotechnological tools, therapeutic agents, and vaccine components.
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