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）：该提案的目的是确定芽孢杆菌物种中大型，低拷贝数质粒的DNA分离机理。通过研究苏云金芽孢杆菌中的质粒pbtoxis，我们确定了一种属于微管蛋白超家族的新型分离蛋白。 Tubz是一种不同的小管蛋白，它聚集了质粒pbtoxis稳定遗传至关重要的动态聚合物。微管蛋白样蛋白通常在毒力质粒上发现，但是它们如何对质粒稳定性有效。我们还确定了枯草芽孢杆菌中参与质粒DNA分离的几个不同的肌动蛋白样蛋白家族。质粒PLS32和ALP7A的阿尔法都组装了聚合物，但它们似乎通过不同的机制将质粒隔离。该提案的目的是了解生化特性，体内组装动力学以及小芽孢杆菌蛋白和肌动蛋白与质粒DNA分离的功能。由于在芽孢杆菌的致病性菌株中（例如炭疽芽孢杆菌的PXO1）中编码了多种毒力因子，因此了解质粒如何从一代中传播到下一代对了解这些关键病毒性确定剂的进化和传播至关重要。 公共卫生相关性：本研究的重点是了解细菌质粒的遗传。质粒在细菌发病机理中起关键作用，因为它们通常是可传播的，并且编码抗生素耐药性和毒力性状，例如毒素和胶囊。因此，这些研究可以帮助鉴定新的狭窄频谱抗生素的靶标，因为阻断质粒稳定性将在某些感染中降低致病性。