LIPIDOMIC ANALYSIS OF MYCOBACTERIUM TUBERCULOSIS

结核分枝杆菌的脂质组学分析

• 批准号: 8363790
• 负责人: Paul R Ortiz De Montellano
• 金额: $ 0.17万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363790
• 关键词: Bacteria; Bacterial Genome; Biochemical Pathway; Biological; Code; Cytochrome P450; Development; Drug Delivery Systems; Enzymes; Fourier transform ion cyclotron resonance; Funding; Genes; Genetic; Genome; Grant; Growth; Individual; Intervention; Knock-out; Label; Lipids; Mass Spectrum Analysis; Metabolism; Mycobacterium tuberculosis; National Center for Research Resources; Pharmaceutical Preparations; Physiological; Principal Investigator; Proteins; Research; Research Infrastructure; Resistance; Resources; Role; Source; Sterols; Tuberculosis; United States National Institutes of Health; comparative; cost; fatty acid metabolism; genome sequencing; interest; lipid metabolism; novel; tuberculosis drugs; tuberculosis treatment

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The global spread of tuberculosis (TB) has been aggravated by the development of strains of the causative bacterium Mycobacterium tuberculosis (Mtb) that are resistant to the leading drugs. New TB therapies are urgently needed, but fortunately recent genome sequence, genetic and protein characterization studies have helped identify novel Mtb drug targets and key biochemical pathways for strategic intervention. In this regard, genes that code for lipid metabolism are a very important part of the bacterial genome, and 8% of the genome is involved in this activity. Of particular interest in the present context are the multiple cytochromes P450 (P450) encoded in the Mtb genome, whose biological roles are not yet understood. To date, physiological roles have been proposed for CYP125 CYP142 and CYP51 in sterol metabolism and for CYP132 in fatty acid metabolism, but none of these roles has been established. In this project, we intend to elucidate the function(s) of Mtb P450 enzymes, including CYP125, CYP130 and CYP141, by comparative analyses of the global lipid profiles of normal Mtb and strains in which the individual P450 enzymes have been knocked out. This comparison will be carried out using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The availability of knockout strains for these P450s makes possible a direct comparison of the lipidomic profiles under different growth and labeling conditions.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 对主要药物产生耐药性的结核分枝杆菌 (Mtb) 菌株的出现加剧了结核病 (TB) 的全球传播。迫切需要新的结核病治疗方法，但幸运的是，最近的基因组序列、遗传和蛋白质特征研究已帮助确定新的结核病药物靶点和战略干预的关键生化途径。在这方面，编码脂质代谢的基因是细菌基因组中非常重要的一部分，8%的基因组参与了这一活动。目前特别感兴趣的是 Mtb 基因组中编码的多种细胞色素 P450 (P450)，其生物学作用尚不清楚。迄今为止，已提出 CYP125、CYP142 和 CYP51 在甾醇代谢中以及 CYP132 在脂肪酸代谢中的生理作用，但这些作用尚未确定。在本项目中，我们打算通过对正常结核分枝杆菌和单个 P450 酶已被敲除的菌株的整体脂质谱进行比较分析，阐明结核分枝杆菌 P450 酶（包括 CYP125、CYP130 和 CYP141）的功能。该比较将使用傅里叶变换离子回旋共振质谱（FT-ICR MS）进行。这些 P450 的敲除菌株的可用性使得可以直接比较不同生长和标记条件下的脂质组学特征。