Transcriptional regulation of GBS capsule biosynthesis

GBS胶囊生物合成的转录调控

• 批准号: 6340373
• 负责人: MICHAEL John CIESLEWICZ
• 金额: $ 4.2万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6340373
• 关键词: Streptococcus agalactiae; bacterial capsules; bacterial genetics; bacterial polysaccharides; carbohydrate biosynthesis; genetic promoter element; genetic transcription; microorganism culture; operon

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.

描述（由申请方提供）：无乳链球菌（B组链球菌或GBS）是新生儿肺炎、败血症和脑膜炎的常见原因。无荚膜GBS突变体在小鼠中表现出降低的毒力，表明荚膜多糖是主要的毒力因子。发现GBS菌株表达九种不同的荚膜血清型Ia、Ib和II-VIII。我们的研究集中在人类感染中最重要的GBS荚膜血清型之一，Ia型。指导Ia型荚膜合成的GBS操纵子由16个基因组成，预计含有两个启动子。第一启动子位于第一基因cpsIaA的上游。预测第二下游启动子位于cpsIaE的上游。非极性cpsIaA缺失突变体在细胞表面表现出降低的胶囊表达，但cpsIaA缺失突变体及其亲本野生型菌株中的单个胶囊链具有相同的分子大小。此外，在cpsIaA缺失突变体中，cpsIaA下游基因的转录被下调。这些结果提示CpsIaA作为转录激活剂起作用。在这个建议中，我们将确定Ia型GBS胶囊操纵子的转录组织和相对启动子强度。此外，我们将确定CpsIaA是否直接调节Ia型荚膜基因的转录。在这个建议中概述的实验将导致更好地了解GBS胶囊生物合成的转录调控。