A STREPTOCOCCAL INACTIVATOR OF HUMAN CHEMOATTRACTANTS

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The primary goal of this project is to better understand the biochemical basis for the propensity of group A streptococci to cause human disease and to evaluate the importance of a newly discovered streptococcal inactivator of complement mediated chemotaxis, designated SCFI, to this process. The human complement serum protein C5a, the primary chemotaxin of inflammatory processes, is specifically cleaved by the peptidase activity associated with SCFI. Studies proposed here will further define the specificity of this unique streptococcal peptidase. Isolation and purification procedures will be optimized employing conventional column chromatography, and high pressure chromatographic methods. Experiments with purified enzyme will evaluate the role of this factor in streptococcal virulence; does it influence the resistance of streptococci to phagocytosis, assist colonization of mucosal tissues or retard the inflammatory response? Mice and rabbits will be used for these experiments. Antisera able to neutralize SCFI activity will be tested for the potential to alter virulence of various streptococcal serotypes. The lack of M type specificity makes this protein a potential candidate for a streptococcal vaccine. This possibility will be tested by immunization of animals with purified SCFI. Various animal models of streptococcal infection will be tried. The immunological response to SCFI in humans will be determined by quantitating antibody in sera from healthy and convalescent individuals with an indirect ELISA assay.