The specific aims of the proposed research are (1) to identify and characterize the binding domain of E. coli type 1 fimbriae, which are responsible for mannose-sensitive binding to a variety of eukaryotic cells, and (2) to investigate the genetic regulation of and environmental effects on fimbrial synthesis. The first project will depend on the isolation and purificaton of fimbrial proteins from both wild-type bacteria that produce normal fimbriae, and mutants that produce aberrent (nonfunctional) fimbriae, should permit identification of the binding region. We will then examine the ability of the binding fragment or antibody to the binding fragment to inhibit bacterial or fimbrial adherence. The second project will employ the techniques of operon fusion, along with other genetic methods, to investigate the positive and negative regulatory signals for fimbrial synthesis. It is hoped that these studies on E. coli fimbriae will shed light on the mechanisms of bacterial adherence and colonization, events of great importance in human infection. Several long-term objectives that may derive from this work include the development of an anti-adherence vaccine with broad spectrum specificity and the development of new lines of antimicrobial chemotherapy that depend on modulation of pathogenicity rather than inhibition of bacterial growth.
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