MECHANISM OF MYCOBACTERIUM TUBERCULOSIS PERSISTENCE

结核分枝杆菌持续存在的机制

• 批准号: 7652988
• 负责人: ADRIE JC STEYN
• 金额: $ 36.59万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-22 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7652988
• 关键词: Affect; Alabama; Alleles; Amino Acids; Anabolism; Area; Attenuated; Bacillus (bacterium); Biological Assay; Biology; Carbon; Cause of Death; Cells; Communities; DNA; DNA Binding; DNA Microarray Chip; DNA-Binding Proteins; Data; Development; Disease; Electron Spin Resonance Spectroscopy; Equilibrium; Event; Exposure to; Faculty; Fatty Acids; Funding; Genetic; Goals; Health system; Homeostasis; Human; Hydroxyl Radical; Hypoxia; Immune response; In Vitro; Inflammatory; Intervention; Iron; Knowledge; Life; Ligation; Lipids; Lung; MMP3 gene; Measurement; Measures; Mediating; Metabolic; Metabolic Pathway; Metabolism; Molecular Profiling; Mus; Mutagenesis; Mutate; Mycobacterium bovis; Mycobacterium tuberculosis; NADH; NADP; Occupations; Oxidation-Reduction; Oxidative Stress; Physiological; Point Mutation; Process; Production; Property; Protein Fragment; Proteins; Public Health; Regulation; Regulon; Resistance; Series; Sigma Factor; Signal Transduction; Sirolimus; Source; Stress; Sulfhydryl Compounds; Sulfur; System; Technology; Time; Transcriptional Activation; Translating; Triglycerides; Tuberculosis; Universities; Work; base; economic impact; genetic regulatory protein; genome-wide; in vivo; mutant; mycobacterial; novel; novel therapeutic intervention; oxidation; prevent; reconstitution; response; sensor; sulfolipids

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. M. tuberculosis (Mtb) is one of the leading causes of death worldwide and claims millions of lives annually. Approximately ~1.7 billion people worldwide are asymptomatically infected with the tubercle bacillus and constitute a major impediment to worldwide public health control measures. Previous work had shown that a point mutation (Arg His) in the 4.2 domain of RpoV, the principal sigma factor in Mycobacterium bovis, is attenuating. Mice infected with MtbwhiB3 showed significantly longer survival times than mice infected with the wild type Mtb. In addition, the lungs of MtbwhiB3-infected mice appeared much less adversely affected. Recent studies have shown that WhiB3 is a 4Fe-4S cluster protein and initiates the metabolic switchover to the preferred in vivo carbon source, fatty acids. We hypothesize that WhiB3 is an intracellular redox sensor that maintains redox homeostasis. To better understand the mechanism of this physiological event, we will identify the WhiB3 amino acids necessary for effective iron-sulfur (Fe-S) reconstitution, and use electron paramagnetic resonance spectroscopy (EPR) to characterize these mutated proteins. We will use genome-wide expression profiling to examine the contribution of WhiB3 in maintaining redox homeostasis, and analyze the metabolite profile of MtbwhiB3. These studies will characterize WhiB3 as a potential target for interventions. The University of Alabama at Birmingham (UAB) is Alabama's largest employer, with more than 18,000 faculty and staff at the university and in the health system, and is responsible for 52,900 full-time equivalent jobs within the university and the community. Eight in every 100 jobs in the Birmingham area, and 2.8 jobs in every 100 jobs in Alabama, are related to UAB. UAB's overall economic impact in the Birmingham metro area exceeds $3 billion annually. Consistent with ARRA goals, this application will create or retain ~7 jobs. 515

在这里输入文本，即应用程序的新抽象信息。本节