LIPIDOMIC ANALYSIS OF MYCOBACTERIUM TUBERCULOSIS

结核分枝杆菌的脂质组学分析

• 批准号: 7957425
• 负责人: Paul R Ortiz De Montellano
• 金额: $ 0.05万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957425
• 关键词: Bacteria; Bacterial Genome; Biochemical Pathway; Biological; Code; Computer Retrieval of Information on Scientific Projects Database; Cytochrome P450; Development; Drug Delivery Systems; Enzymes; Fourier transform ion cyclotron resonance; Funding; Genes; Genetic; Genome; Grant; Growth; Individual; Institution; Intervention; Knock-out; Label; Lipids; Mass Spectrum Analysis; Metabolism; Mycobacterium tuberculosis; Pharmaceutical Preparations; Physiological; Proteins; Research; Research Personnel; Resistance; Resources; Role; Source; Sterols; Tuberculosis; United States National Institutes of Health; Work; comparative; fatty acid metabolism; genome sequencing; interest; lipid metabolism; novel; tuberculosis treatment

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. This work is supported by NIH grant AI074824.

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