The long-term goal of this study is to understand the molecular, biochemical, and immunologic factors that contribute to the pathogenesis of Enterococcus faecalis and E.faecium infections, with special emphasis on multiply antibiotic-resistant enterococci. Further understand of the interaction of these bacteria with the human host defense system will give new insights into how to prevent disease due to enterococcal infections. The molecular and biochemical studies will concentrate on isolating and characterizing likely capsular polysaccharides of enterococci which will culminate in deterring the monosaccharide components and linkages in these antigens. Electron microscopy using antibodies specific to isolated polysaccharides will determine if the materials are extracellular capsules. The immunologic studies will focus on whether the isolated antigens are targets for protective immune responses. In this study between three and five serologically distinct antigens will be purified and characterized chemically and immunologically. A mouse peritonitis/sepsis model and a neonatal mouse model will be used to evaluate the effectiveness of antibodies specific for the capsular polysaccharides in prevention of enterococcal infections. Active immunization with purified capsule and passive protection using capsule-specific antibodies will be tested in this models. By the end of these studies we expect to have a clear understanding of the occurrence, biochemistry and immunology of capsular polysaccharides of enterococci, a definition of their role in pathogenesis of enterococcal infections, and the potential to develop immunotherapies to prevent infection in patient at-risk for this disease.
| Harbarth, S; Albrich, W; Goldmann, D A et al. (2001) Control of multiply resistant cocci: do international comparisons help? Lancet Infect Dis 1:251-61 |
| Wang, Y; Huebner, J; Tzianabos, A O et al. (1999) Structure of an antigenic teichoic acid shared by clinical isolates of Enterococcus faecalis and vancomycin-resistant Enterococcus faecium. Carbohydr Res 316:155-60 |
