This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fernie-King, B. A. Articles by Lachmann, P. J. Search for Related Content PubMed PubMed Citation Articles by Fernie-King, B. A. Articles by Lachmann, P. J.

 Previous Article  |  Next Article 

Infection and Immunity, September 2002, p. 4908-4916, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.4908-4916.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Streptococcal Inhibitor of Complement Inhibits Two Additional Components of the Mucosal Innate Immune System: Secretory Leukocyte Proteinase Inhibitor and Lysozyme

Microbial Immunology Group, Centre for Veterinary Science, University of Cambridge, Cambridge, United Kingdom

Received 8 March 2002/ Returned for modification 9 May 2002/ Accepted 10 June 2002

Streptococcal inhibitor of complement (SIC) is a 31-kDa extracellular protein of a few, very virulent, strains of Streptococcus pyogenes (particularly M1 strains). It is secreted in large quantities (about 5 mg/liter) and inhibits complement lysis by blocking the membrane insertion site on C5b67. We describe investigations into the interaction of SIC with three further major components of the innate immune system found in airway surface liquid, namely, secretory leukocyte proteinase inhibitor (SLPI), lysozyme, and lactoferrin. Enzyme-linked immunosorbent assays showed that SIC binds to SLPI and to both human and hen egg lysozyme (HEL) but not to lactoferrin. Studies using ¹²⁵I-labeled proteins showed that SIC binds approximately two molecules of SLPI and four molecules of lysozyme. SLPI binding shows little temperature dependence and a small positive enthalpy, suggesting that the binding is largely hydrophobic. By contrast, lysozyme binding shows strong temperature dependence and a substantial negative enthalpy, suggesting that the binding is largely ionic. Lysozyme is precipitated from solution by SIC. Further studies examined the ability of SIC to block the biological activities of SLPI and lysozyme. An M1 strain of group A streptococci was killed by SLPI, and the antibacterial activity of this protein was inhibited by SIC. SIC did not inhibit the antiproteinase activity of SLPI, implying that there is specific inhibition of the antibacterial domain. The antibacterial and enzymatic activities of lysozyme were also inhibited by SIC. SIC is the first biological inhibitor of the antibacterial action of SLPI to be described and may prove to be an important tool for investigating this activity in vivo. Inhibition of the antibacterial actions of SLPI and lysozyme would be advantageous to S. pyogenes in establishing colonization on mucosal surfaces, and we propose that this is the principal function of SIC.

Editor: E. I. Tuomanen

This article has been cited by other articles:

• Manolov, T., Tan, T. T., Forsgren, A., Riesbeck, K. (2008). Moraxella-Dependent {alpha}1-Antichymotrypsin Neutralization: A Unique Virulence Mechanism. Am. J. Respir. Cell Mol. Bio. 38: 609-617 [Abstract] [Full Text]  
• Sagar, V., Kumar, R., Ganguly, N. K., Menon, T., Chakraborti, A. (2007). DRS Is Far Less Divergent than Streptococcal Inhibitor of Complement of Group A Streptococcus. J. Bacteriol. 189: 2933-2935 [Abstract] [Full Text]  
• Ivanov, I. B., Gritsenko, V. A., Kuzmin, M. D. (2006). Staphylococcal secretory inhibitor of platelet microbicidal protein is associated with prostatitis source.. J Med Microbiol 55: 1645-1648 [Abstract] [Full Text]  
• Shelburne, S. A. III, Granville, C., Tokuyama, M., Sitkiewicz, I., Patel, P., Musser, J. M. (2005). Growth Characteristics of and Virulence Factor Production by Group A Streptococcus during Cultivation in Human Saliva. Infect. Immun. 73: 4723-4731 [Abstract] [Full Text]  
• Binks, M. J., Fernie-King, B. A., Seilly, D. J., Lachmann, P. J., Sriprakash, K. S. (2005). Attribution of the Various Inhibitory Actions of the Streptococcal Inhibitor of Complement (SIC) to Regions within the Molecule. J. Biol. Chem. 280: 20120-20125 [Abstract] [Full Text]  
• Binks, M., Sriprakash, K. S. (2004). Characterization of a Complement-Binding Protein, DRS, from Strains of Streptococcus pyogenes Containing the emm12 and emm55 Genes. Infect. Immun. 72: 3981-3986 [Abstract] [Full Text]  
• Binks, M., McMillan, D., Sriprakash, K. S. (2003). Genomic Location and Variation of the Gene for CRS, a Complement Binding Protein in the M57 Strains of Streptococcus pyogenes. Infect. Immun. 71: 6701-6706 [Abstract] [Full Text]  
• Frick, I.-M., Akesson, P., Rasmussen, M., Schmidtchen, A., Bjorck, L. (2003). SIC, a Secreted Protein of Streptococcus pyogenes That Inactivates Antibacterial Peptides. J. Biol. Chem. 278: 16561-16566 [Abstract] [Full Text]  
• Fernie-King, B, Seilly, D J, Davies, A, Lachmann, P J (2002). Subversion of the innate immune response by micro-organisms. Ann Rheum Dis 61: ii8-12 [Full Text]