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
Copyright © 2015 by The American Society for BioMedicine and BM-Publisher, Inc.
References
- Yuste J, Botto M, Paton JC, Holden DW, Brown JS. Additive inhibition of complement deposition by pneumolysin and PspA facilitates streptococcus pneumoniae septicemia. J Immunol 2005;175: 1813-1819.
https://doi.org/10.4049/jimmunol.175.3.1813 - Ali YM, Lynch NJ, Haleem KS, Fujita T, Endo Y, et al. The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection. PLoS Pathog 2012; 8: e1002793.
https://doi.org/10.1371/journal.ppat.1002793 - Awada A, van der Auwera P, Meunier F. et al. Streptococcal and enterococcal bacteremia in patients with cancer. Clin. Infect. Dis 1992;15:33-48.
https://doi.org/10.1093/clinids/15.1.33 - Thiel S. Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and associated proteins. Mol. Immunol 2007;44:3875-388.
https://doi.org/10.1016/j.molimm.2007.06.005 - Kjaer TR, Hansen AG, Sorensen UB, Nielsen O, Thiel S, Jensenius JC. Investigations on the pattern recognition molecule M-ficolin: quantitative aspects of bacterial binding and leukocyte association. J. Leukoc. Biol 2011; 90:425-437.
https://doi.org/10.1189/jlb.0411201 - Park IH, Pritchard DG, Cartee R, Brandao A, Brandileone MC, Nahm MH. Discovery of a new capsular serotype (6C) within serogroup 6 of Streptococcus pneumoniae. J. Clin. Microbiol 2007; 45:1225-1233.
https://doi.org/10.1128/JCM.02199-06 - Frederiksen PD, Thiel S, Jensen L, Hansen AG, Matthiesen F, Jensenius JC. Quantification of mannan-binding lectin. J. Immunol. Methods 2006; 315:49-60.
https://doi.org/10.1016/j.jim.2006.07.001 - Endo Y, Takahashi M, Iwaki D, Ishida Y, Nakazawa N, Kodama T, Matsuzaka T, Kanno K, Liu Y, Tsuchiya K, Kawamura I, Ikawa M, Waguri S, Wada I, Matsushita M, Shwaeble WJ, Fujita T. Mice deficient in ficolin, a lectin complement pathway recognition molecule, are susceptible to Streptococcus pneumoniae infection. J. Immunol 2012; 189:5860-5866.
https://doi.org/10.4049/jimmunol.1200836 - Wessels MR, Butko P, Ma M, Warren HB, Lage AL, Carroll MC. Studies of group B streptococcal infection in mice deficient in complement component C3 or C4 demonstrate an essential role for complement in both innate and acquired immunity.Proc Natl Acad Sci U S A. 1995;92(25):11490-4.
https://doi.org/10.1073/pnas.92.25.11490 - Ochel A1, Rohde M, Chhatwal GS, Talay SR. The M1 Protein of Streptococcus pyogenes Triggers an Innate Uptake Mechanism into Polarized Human Endothelial Cells. J Innate Immun. 2014 Jan 31.
https://doi.org/10.1159/000358085 - hang JC, LaSarre B, Jimenez JC, Aggarwal C, Federle MJ. Two group A streptococcal peptide pheromones act through opposing Rgg regulators to control biofilm development. PLoS Pathog. 2011;7:e1002190.
https://doi.org/10.1371/journal.ppat.1002190 - Gardan R, Besset C, Guillot A, Gitton C, Monnet V. The oligopeptide transport system is essential for the development of natural competence in Streptococcus thermophilus strain LMD-9. J. Bacteriol 2009; 191:4647-4655.
https://doi.org/10.1128/JB.00257-09 - Jones N,et al. Multilocus sequence typing system for group B streptococcus. J. Clin. Microbiol 2003; 41:2530-2536.
https://doi.org/10.1128/JCM.41.6.2530-2536.2003 - Sandgren A, Sjostrom K, Olsson-Liljequist B, Christensson B, Samuelsson A, et al. Effect of clonal and serotype-specific properties on the invasive capacity of Streptococcus pneumoniae. J Infect Dis 12004; 89: 785-796.
https://doi.org/10.1086/381686 - Kim JO, Weiser JN. Association of intrastrain phase variation in quantity of capsular polysaccharide and teichoic acid with the virulence of Streptococcus pneumoniae. J Infect Dis 1998; 177: 368-377.
https://doi.org/10.1086/514205 - onsson G, Truedsson L, Sturfelt G, Oxelius VA, Braconier JH, et al. Hereditary C2 deficiency in Sweden: frequent occurrence of invasive infection, atherosclerosis, and rheumatic disease. Medicine (Baltimore) 2005; 84: 23-34.
https://doi.org/10.1097/01.md.0000152371.22747.1e - Xu Y, Ma M, Ippolito GC, Schroeder HW Jr, Carroll MC, et al. Complement activation in factor D-deficient mice. Proc Natl Acad Sci USA 2001; 98: 14577-14582.
https://doi.org/10.1073/pnas.261428398 - Walport MJ. Complement- Second of Two Parts. The New England Journal of Medicine 2001; 344:1140-1144.
https://doi.org/10.1056/NEJM200104123441506 - Neth O, Jack DL, Dodds AW, Holzel H, Klein NJ, et al. Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition. Infect Immun 2000; 68: 688-693.
https://doi.org/10.1128/IAI.68.2.688-693.2000 - Goldstein N . Planktonics or Biofilms infections? American journal of BioMedicine 2013; 1(1):1-3.
https://doi.org/10.18081/ajbm/2333-5106-013-11/1-3
Research Article
DOI: http://dx.doi.org/10.18081/2333-5106/015-3/473-481
American Journal of BioMedicine 2015, Volume 3, Issue 3, pages 141-153
Received February 11, 2015; Accepted July; 11, 2015, Published August 06, 2015