Group B Streptococcus (GBS): is a leading cause of serious infection in newborns and pregnant women, and in adults immunologically impaired by liver disease, diabetes and malignancy. GBS contain a family of immunogenic surface proteins that are characterized by the presence of long tandemly-repeated elements, the prototype of which is the alpha C protein. Previous work has demonstrated that variation in the number of tandem repeats in the gene for the alpha C protein (bca), alters the antigenicity of the protein and the virulence of the strain in the presence of specific antibody. Tandem repeat deletion in the alpha C protein allows antigenic variation and may thus serve as a virulence mechanism in GBS. The molecular mechanism by which excision of tandem repeat units in bca is accomplished is unknown. Identification of the molecular factors involved in tandem repeat deletion of broader interest as tandem repeat sequences of DNA are found in both prokaryotic and eukaryotic genomes, and variation in these sequences is associated both with changes in bacterial virulence and the genesis of inherited human diseases. Previous work by the applicant has demonstrated that inactivation of recA, the principal gene involved in bacterial homologous recombination, does not affect tandem repeat deletion in GBS. The scientific goals of this project are to identify genes involved in tandem repeat deletion in GBS, and to determine the role of conserved nucleotide sequences within repeats in directing tandem repeat deletion. To meet these goals, a plasmid -based reporter system will be constructed to complement studies of chromosomal tandem repeat deletion. The training goal of this project is to prepare the applicant for a career in bacterial genetic research by providing didactic education and the opportunity to develop laboratory expertise in this rapidly evolving field.
