Transcriptional regulation of GBS capsule biosynthesis

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DESCRIPTION (provided by applicant): Streptococcus agalactiae (Group B Streptococcus or GBS) is a common cause of neonatal pneumonia, sepsis and meningitis. Acapsular GBS mutants exhibit decreased virulence in mice suggesting that the capsular polysaccharide is a major virulence factor. Strains of GBS are found to express nine different capsule serotypes, Ia, Ib and II-VIII. We have focused our study on one of the most important in GBS capsule serotypes in human infection, type Ia. The GBS operon that directs synthesis of the type Ia capsule consists of 16 genes and is predicted to contain two promoters. The first promoter is upstream of the first gene, cpsIaA. A second, downstream promoter is predicted to lie upstream of cpsIaE. A non-polar cpsIaA deletion mutant exhibits decreased capsule expression at the surface of the cell, yet individual capsule chains in the cpsIaA deletion mutant and its parent wild-type strain are the same molecular size. Additionally, transcription of genes downstream of cpsIaA is down-regulated in a cpsIaA deletion mutant. These results are suggestive of CpsIaA acting as a transcriptional activator. In this proposal we will determine the transcriptional organization and relative promoter strength of the type Ia GBS capsule operon. In addition, we will determine if CpsIaA directly modulates transcription of the type Ia capsule genes. Experiments outlined in this proposal will lead to a better understanding of transcriptional regulation of GBS capsule biosynthesis.