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Steroid Hormone Biosynthesis by M.tb

M.tb 的类固醇激素生物合成

基本信息

批准号：
8230485
负责人：
NICOLE S SAMPSON
金额：
$ 19.27万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-02-15 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8230485
关键词：
Acetates Agonist Anabolism Antibiotics Attenuated Bacteria Bacteriophages Biology Carbon Cells Cholesterol Cholesterol Homeostasis Complex Development Down-Regulation Drug Delivery Systems Drug resistance Energy-Generating Resources Environment Enzyme Gene Enzymes Extreme drug resistant tuberculosis Fatty Acids Genes Glucocorticoids Goals Growth Hormones Human Immune response Immune system Immunology Immunomodulators In Vitro Infection Lipids Lung Metabolic Pathway Metabolism Modeling Mole the mammal Multi-Drug Resistance Multidrug-Resistant Tuberculosis Mus Mycobacterium tuberculosis National Institute of Allergy and Infectious Disease Nuclear Hormone Receptors Organism Pathway interactions Pharmaceutical Preparations Pharmacologic Substance Pharmacopoeias Play Population Production Propionates Research Rifampin Role Signal Pathway Source Staging Structure Targeted Research Tars Testing Tuberculosis Virulence Virulent Vitamin D3 Receptor Work World Health Organization base chemotherapeutic agent combat in vivo isoniazid macrophage novel strategies pathogen public health relevance research study small molecule steroid hormone biosynthesis tuberculosis drugs

项目摘要

DESCRIPTION (provided by applicant): The World Health Organization estimates that 2 million people die every year from tuberculosis and that 30% of the world's population is infected. Multi-drug resistant organisms are widespread and extensively drug resistant organisms are emerging. New approaches are required to combat these virulent and drug resistant organisms (MDR/XDR TB). The proposed experiments are aimed at characterizing metabolites produced by M. tb using cholesterol as a starting material. The hypothesis is that M. tb transforms cholesterol to hormones that regulate the host immune system. The corresponding enzymatic activities that catalyze hormone synthesis represent new targets for anti-MDR-TB pharmaceutical development. The aim of this work is to identify candidate immunomodulatory metabolites produced during growth of M. tb on cholesterol and in macrophages in order to drive the identification of the genes and corresponding enzymes responsible for their formation. PUBLIC HEALTH RELEVANCE: The proposed research fits within the targeted research needs of NIAID that seeks the development of new chemotherapeutic agents against MDR/XDR TB. These experiments will provide a basis for discovering the structure of metabolites that regulate the host immune response to TB and guide development of new antibiotics that would be effective against all forms of TB including MDR/XDR TB.

描述(申请人提供)：世界卫生组织估计，每年有200万人死于结核病，世界人口的30%受到感染。多重耐药的生物很普遍，而且广泛耐药的生物正在出现。需要新的方法来抗击这些毒力和抗药性生物体(耐多药/广泛耐药结核)。拟议的实验旨在以胆固醇为起始物质来表征结核分枝杆菌产生的代谢物。假设是结核分枝杆菌将胆固醇转化为调节宿主免疫系统的激素。相应的催化激素合成的酶活性代表了抗耐多药结核病药物开发的新靶点。这项工作的目的是鉴定结核分枝杆菌在胆固醇和巨噬细胞上生长过程中产生的候选免疫调节代谢物，以推动对负责它们形成的基因和相应酶的鉴定。与公共卫生相关：拟议的研究符合NIAID的目标研究需求，即寻求开发针对MDR/XDR结核病的新化疗药物。这些实验将为发现调节宿主对结核病的免疫反应的代谢物的结构提供基础，并指导新抗生素的开发，这些抗生素将对包括耐多药/广泛耐药结核病在内的所有形式的结核病有效。