DNA segregation during Bacillus growth and development

芽孢杆菌生长和发育过程中的 DNA 分离

• 批准号: 8310033
• 负责人: JOSEPH A POGLIANO
• 金额: $ 32.22万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8310033
• 关键词: ATP Hydrolysis; Actins; Antibiotic Resistance; Antibiotics; Bacillus (bacterium); Bacillus anthracis; Bacillus subtilis; Bacillus thuringiensis; Bacterial DNA; Bacterial Genome; Binding Sites; Biochemical; Caliber; Cells; Collaborations; Coupled; Cytoskeletal Proteins; DNA; DNA-Binding Proteins; Electrons; Elements; Escherichia coli; Evolution; Family; Filament; Generations; Goals; Growth; Growth and Development function; Hydrolysis; In Vitro; Infection; Inherited; Life; Mediating; Microscopy; Modeling; Molecular Genetics; Movement; Nucleotides; Operon; Pathogenesis; Pathogenicity; Plasmids; Play; Polymers; Property; Proteins; Reporting; Structure; Study models; System; Testing; Time; Toxin; Tubulin; Virulence; Virulence Factors; capsule; genetic analysis; in vivo; mutant; novel; plasmid DNA; polymerization; protein expression; public health relevance; research study; segregation; time use; trait

DESCRIPTION (provided by applicant): The goal of this proposal is to identify the mechanisms of DNA segregation for large, low copy number plasmids in Bacillus species. From studying plasmid pBtoxis in Bacillus thuringiensis, we identified a novel segregation protein belonging to the tubulin superfamily. TubZ is a divergent tubulin like protein that assembles dynamic polymers essential for the stable inheritance of plasmid pBtoxis. Tubulin-like proteins are commonly found on Bacillus virulence plasmids, but how they contribute to plasmid stability is unknown. We have also identified several families of divergent actin-like proteins involved in plasmid DNA segregation in Bacillus subtilis. AlfA of plasmid pLS32 and Alp7A both assemble polymers, but they appear to segregate plasmids by different mechanisms. The goal of this proposal is to understand the biochemical properties, in vivo assembly dynamics, and the functions of Bacillus tubulins and actins involved in plasmid DNA segregation. Since a wide variety of virulence factors are encoded on plasmids in pathogenic strains of Bacillus, such as pXO1 of B. anthracis, understanding how plasmids are transmitted from one generation to the next is important for understanding the evolution and spread of these key virulence determinants. PUBLIC HEALTH RELEVANCE: This study focuses on understanding how bacterial plasmids are inherited. Plasmids play key roles in bacterial pathogenesis, as they are often transmissible and encode antibiotic resistance and virulence traits, such as toxins and capsules. These studies could therefore help identify targets for new narrow spectrum antibiotics, since blocking plasmid stability will in certain infections decrease pathogenicity.

描述（由申请人提供）：本提案的目标是确定芽孢杆菌属中大、低拷贝数质粒的 DNA 分离机制。通过研究苏云金芽孢杆菌中的质粒 pBtoxis，我们鉴定了一种属于微管蛋白超家族的新型分离蛋白。 TubZ 是一种发散的微管蛋白样蛋白质，可组装对质粒 pBtoxis 稳定遗传至关重要的动态聚合物。微管蛋白样蛋白常见于芽孢杆菌毒力质粒上，但它们如何促进质粒稳定性尚不清楚。我们还鉴定了几个参与枯草芽孢杆菌中质粒 DNA 分离的不同肌动蛋白样蛋白家族。质粒 pLS32 的 AlfA 和 Alp7A 都组装聚合物，但它们似乎通过不同的机制分离质粒。该提案的目标是了解芽孢杆菌微管蛋白和肌动蛋白参与质粒 DNA 分离的生化特性、体内组装动力学以及功能。由于芽孢杆菌病原菌株的质粒上编码了多种毒力因子，例如炭疽芽孢杆菌的 pXO1，因此了解质粒如何从一代传播到下一代对于了解这些关键毒力决定因素的进化和传播非常重要。 公共健康相关性：这项研究的重点是了解细菌质粒是如何遗传的。质粒在细菌发病机制中发挥着关键作用，因为它们通常具有传播性并编码抗生素抗性和毒力特征，例如毒素和荚膜。因此，这些研究可以帮助确定新的窄谱抗生素的靶标，因为阻断质粒稳定性将在某些感染中降低致病性。