Small RNA regualtors of the B. anthracis plasmid pXO1

炭疽芽孢杆菌质粒 pXO1 的小 RNA 调节子

• 批准号: 6964937
• 负责人: KEITH E WEAVER
• 金额: $ 19.88万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6964937
• 关键词: Bacillus anthracis; bacteria infection mechanism; bacterial genetics; bacterial toxins; bioterrorism /chemical warfare; computer data analysis; gene expression; genetic transcription; growth inhibitors; intermolecular interaction; microorganism growth; nucleic acid hybridization; nucleic acid purification; plasmids; polymerase chain reaction; small nuclear RNA; virulence

DESCRIPTION (provided by applicant): Bacillus anthracis is the causative agent of anthrax and a biodefense category A priority pathogen. Wild type B. anthracis carries two plasmids, pXO1 and pXO2, both of which are absolutely required for production of disease. pXO1 encodes the components of the anthrax toxin and pXO2 encodes the genes for production of the poly-D-glutamic acid capsule, both of which are essential virulence factors. Most of the research on these plasmids has focused on the toxin and capsule genes and their regulation, but little is known about the biology of the plasmids themselves. The experiments described in this proposal are designed to identify and characterize small RNAs that may be involved in regulation of pXO1 plasmid-encoded functions. Emphasis will initially focus on plasmid maintenance functions, including those required for replication and stable inheritance, since small RNAs frequently regulate these functions in other systems. However, work in other bacteria has clearly shown that RNA-mediated regulation has been underappreciated in prokaryotic systems and probably plays a much more important role in regulatory circuits than previously imagined. Because of this, procedures developed to examine the role of small RNAs in controlling plasmid maintenance will be expanded to screen the entire plasmid for RNAs that may mediate other regulatory aspects of plasmid function, including toxin production. After potential regulatory RNAs have been located, their targets will be identified and their role in regulating those targets will be determined. Detailed studies will be conducted to determine the molecular mechanisms of regulation of these small RNAs. It is hoped that by identifying RNA controlled targets of plasmid function, compounds can be developed to interfere with these functions and thereby "detoxify" the organism. Furthermore, determination of the rules of RNA regulation in this system will pave the way for further study of regulatory RNAs that may be encoded on pXO2 or the B. anthracis chromsome.

描述（由申请人提供）：炭疽芽孢杆菌是炭疽的病原体，是生物防御A类优先病原体。野生型B。炭疽杆菌携带两种质粒pXO 1和pXO 2，这两种质粒都是产生疾病所必需的。 pXO 1编码炭疽毒素的组分，pXO 2编码产生聚-D-谷氨酸荚膜的基因，两者都是必需的毒力因子。大多数关于这些质粒的研究都集中在毒素和胶囊基因及其调控上，但对质粒本身的生物学知之甚少。本提案中描述的实验旨在鉴定和表征可能参与调节pXO 1质粒编码功能的小RNA。重点将首先集中在质粒维持功能，包括复制和稳定遗传所需的功能，因为小RNA经常在其他系统中调节这些功能。然而，在其他细菌中的工作已经清楚地表明，RNA介导的调节在原核系统中被低估，并且可能在调节回路中发挥比以前想象的更重要的作用。正因为如此，开发的程序来检查小RNA在控制质粒维持的作用将被扩展到筛选整个质粒的RNA，可能介导质粒功能的其他调控方面，包括毒素的产生。在定位潜在的调控RNA之后，将鉴定它们的靶点，并确定它们在调节这些靶点中的作用。将进行详细的研究，以确定这些小RNA调控的分子机制。人们希望通过鉴定RNA控制的质粒功能靶点，开发出干扰这些功能的化合物，从而对生物体进行“解毒”。此外，该系统中RNA调控规律的确定将为进一步研究pXO 2或B上可能编码的调控RNA铺平道路。炭疽菌染色体。