Enterococcus faecalis can cause a severe form of endocarditis with a high fatality rate. Treatment of this disease is complicated by the high level of intrinsic and acquired resistance of this organism to antibiotics. A plasmid-encoded surface protein called Asc10 mediates formation of bacterial aggregates, in which plasmid transfer occurs at high frequency. Asc10 enhances the virulence of E. faecalis in experimental endocarditis, and plasmids encoding this type of protein are common in clinical isolates. Expression of Asc10 in the mammalian host is induced by a host factor. Analysis of the structure/function relationships in this protein have shown that the functional domain involved in bacterial aggregation also mediates virulence properties associated with the protein. The proposed experiments seek to define the mechanisms by which specific molecular interactions between Asc10 and host components contribute to the disease process. Analysis of gene expression profiles of the host and pathogen during infections will be carried out.
The specific aims i nclude: 1) Determine the specific biological activities of Asc10 affecting E. faecalis virulence. 2) Determine the functional domains of Asc10 that confer the activities identified in Aim 1. 3) Examine the expression of bacterial and host genes during the course of infections.
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