The association of acute rheumatic fever and acute glomerulonephritis with antecedent group A streptococcal infections has been well documented. Cross-reactions between membrane from different types and strains of streptococci and human heart, brain and kidney tissue have been shown. The main objective of this study is to continue an in depth analysis of the streptococal membrane with particular emphasis on the relation(s) of antigenic and chemical composition to pathogenesis. Initially we will determine the effect of various conditions of media and growth rate on the qualitative and quantitative appearance of components of the membrane. Since distinctions have been made between skin and throat strains as well as rheumatogenic and nephritogenic strains, the membranes from these groups will be compared by two dimensional electrophoresis and immunological analysis. In addition, the effect of selective pressure on the components of interest will be determined. Once the above studies are underway, monoclonal antibodies to specific antigens will be produced using hybridoma technology. Furthermore, the patients's humoral immune response to the membranes components will also be analyzed. Finally, the cross-reactive antigens, the hyaluronic acid biosynthesis complex, the lipoteichoic acid deacylase, and the components unique to each group of strains are to be studied and charaterized. This study will also generate data on the basic structure and function of the streptococcal membrane. Identification of antigenic and enzymatic components of the membrane has received little attention in other laboratories. This study should yield important new information on the similarities and/or dissimilarities between this pathogen and non-pathogens whose membranes have received closer scrutiny. In the United States, rheumatic heart disease is reported to affect about 100,000 children and 1.7 million adults with over 13,000 deaths per year. In the third world nations, rheumatic fever is still a major public health problem. While there is no absolute figure on the incidence of acute poststreptococcal glomerulonephritis, endemic cases of skin nephritis still occur in many places throughout the world.
| van de Rijn, I; Drake, R R (1992) Analysis of the streptococcal hyaluronic acid synthase complex using the photoaffinity probe 5-azido-UDP-glucuronic acid. J Biol Chem 267:24302-6 |
| Dougherty, B A; van de Rijn, I (1992) Molecular characterization of a locus required for hyaluronic acid capsule production in group A streptococci. J Exp Med 175:1291-9 |
| Triscott, M X; van de Rijn, I (1986) Solubilization of hyaluronic acid synthetic activity from streptococci and its activation with phospholipids. J Biol Chem 261:6004-9 |
