DNA segregation during Bacillus growth and development

描述（由申请方提供）：本提案的目的是确定芽孢杆菌属中大、低拷贝数质粒的DNA分离机制。通过对苏云金芽孢杆菌质粒pBtoxis的研究，我们发现了一个属于微管蛋白超家族的分离蛋白。TubZ是一种趋异微管蛋白样蛋白，其组装质粒pBtoxis稳定遗传所必需的动态聚合物。微管蛋白样蛋白通常存在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。我们还确定了几个家庭的分歧肌动蛋白样蛋白参与质粒DNA分离在枯草芽孢杆菌。质粒pLS 32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。本提案的目的是了解的生化特性，在体内组装动力学，以及参与质粒DNA分离的芽孢杆菌微管蛋白和肌动蛋白的功能。由于芽孢杆菌致病菌株的质粒上编码有多种毒力因子，如B的pXO 1。在炭疽病中，了解质粒如何从一代传递到下一代，对于了解这些关键毒力决定因素的进化和传播非常重要。 公共卫生相关性：这项研究的重点是了解细菌质粒是如何遗传的。质粒酶在细菌发病机制中发挥关键作用，因为它们通常是可传播的，并编码抗生素抗性和毒力性状，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点，因为阻断质粒稳定性将在某些感染中降低致病性。

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.