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Role of alkaline protease in activation of viridans streptococci complement system pathway

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American Journal of BioMedicine  Volume 2, Issue 6, pages 650-664, June 2014


Emily V Baker; David J Edwards; Rebecca  B Schulz; Michael  F Hirama

Abstract

Viridans streptococci are a grouping of multiple streptococcal species which do not possess Lancefield antigens, are alpha-hemolytic, and result in infective endocarditis. Despite intensive care with antimicrobial therapy, the mortality has remained high for these infections and post infection squeal. All the pathways of complement system culminate in the formation of C3 convertase enzymes that mediate deposition of C3b on foreign surfaces. The goal of this study, to assay interferes between alkaline protease (AprA) of viridans streptococci and complement activation. Our data found that alkaline protease potently blocked phagocytosis of viridans streptococci by neutrophils the AprA specifically blocked C3b deposition via 2-pathways; the classical and lectin pathways. Serum degradation assays revealed that AprA degrades both human C1s and C2. However, repletion assays demonstrated that the mechanism of action for complement inhibition is cleavage of C2. These results suggest a novel viridans streptococci mechanism, through AprA interferes with complement system pathway activation via cleavage of C2.

Keywords: Viridans streptococci; Alkaline protease; Compement system; Classical pathway; Lectin pathway


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