The focus of the proposed studies is to develop a detailed classification for type II IgG-binding proteins expressed by group A streptococci and to understand the role of these molecules in streptococcal infection or post-infection sequelae. The initial focus will be to develop serological and gene probes to analyze the qualitative and quantitative expression of different forms of IgG-binding protein(s) expressed by group A strains. Once a detailed classification system has been established, these techniques will be applied to characterize the type II IgG-binding proteins expressed on fresh clinical isolates of group A streptococci in order to determine whether there is an association between the qualitative or quantitative expression of IgG-binding proteins and the course of infection of post-infection sequelae in the patient from which the strain was recovered. The biological activities of IgG-binding proteins will be explored using a variety of in vitro and in vivo assay systems. These studies will involve group A strains with defined IgG-binding protein expression as well as examining the effect of insertion of type II IgG-binding protein gene(s) into an IgG-binding protein negative S. gordonii Challis strain. The in vitro system will measure the ability of bacteria expressing type II IgG-binding proteins to survive in human blood while the in vivo system will focus on the ability of the bacteria to establish lethal infections when injected into the skin of mice. These studies will be designed to document the importance of expression of type II IgG-binding proteins. The potential role for an M protein IgG-binding protein hybrid molecule in the formation of immune complexes that could contribute to post-streptococcal glomerulo-nephritis will also be examined. Taken together, these studies of type II IgG-binding proteins should yield new information on the diversity of these molecules and their potential role in establishing invasive streptococcal infections as well as their possible contributions to post-infection sequelae.
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