We request continuing support for our molecular studies of fibronectin (Fn) and fibrinogen (Fib) binding bacterial adhesins. The adhesins present on Gram-positive bacteria such as Staphylococcus aureus and various streptococcal species belong to a family of adhesins that we have called MSCRAMMs, (Microbial Surface Components Recognizing Adhesive Matrix Molecules). The goals for the proposed studies are to determine the structures of the already localized ligand binding sites of the Fn binding MSCRAMMs and the domain(s) recognized in Fn;, We will also initiate an immunological characterization of the MSCRAMMs using a monoclonal antibody approach. The gene encoding the major Fib binding MSCRAMM from S. aureus was recently cloned and sequenced. We will now locate and characterize the active site as well as define the domain recognized in Fib. In these studies, we are using a combination of molecular biological and biochemical techniques. The results of our studies will provide a detailed molecular characterization of the ligand interactions of Fib and Fn binding MSCRAMMs, which represent an early step in the molecular pathogenesis of many infections caused by staphylococcal and streptococcal species. Hence this information will provide the basis for new therapeutic strategies to prevent and treat infections which is much needed particularly at a time when these bacterial species are developing resistance to multiple types of antibiotics.
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