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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 结核病（TB）的全球扩散因抗性药物耐药性的结核分枝杆菌（MTB）的菌株的发展而加剧了。迫切需要新的结核病疗法，但幸运的是，最近的基因组序列，遗传和蛋白质表征研究有助于确定新型的MTB药物靶标和关键的战略干预生化途径。在这方面，脂质代谢代码的基因是细菌基因组中非常重要的一部分，并且8％的基因组参与了这种活性。在当前情况下，特别感兴趣的是MTB基因组中编码的多个细胞色素P450（P450），其生物学作用尚未了解。迄今为止，已经提出了CYP125 CYP142和CYP51在固醇代谢中和CYP132在脂肪酸代谢中提出的生理作用，但是这些作用均未确定。在该项目中，我们打算通过对正常MTB的全局脂质谱和菌株的比较分析来阐明MTB P450酶的功能，包括CYP125，CYP130和CYP141的功能，其中已将单个P450酶的菌株击倒。该比较将使用傅立叶转化离子回旋共振质谱法（FT-ICR MS）进行。这些P450的基因敲除菌株的可用性使得在不同的生长和标记条件下的脂质组谱直接比较。