MTB--MYCOLIC ACID BIOSYNTHETIC AND REGULATORY GENES

描述（改编自申请人的摘要）：结核病具有 被归类为新发和再发传染病。 有助于其公共卫生的重要性是共存的 艾滋病大流行的发展和耐药 结核分枝杆菌菌株。这让人们认识到 需要更多地了解人体的基本代谢途径， 生物体的发展提供了事实依据，新的 抗生素这个项目解决了这个问题，提出了实验 旨在识别代谢途径的生物合成成分 分枝菌酸是M.结核细胞壁 该研究计划要求使用两种新技术， “后基因组时代”：使用完整的注释M.结核病基因组 和mRNA基因反应谱的微阵列竞争 杂交方法基于微阵列的结果将得到以下补充： 生物化学和突变研究进行了合作，博士。 分别是帕特里克·布伦南和布丽吉特·吉奎尔。在终端 本研究的第一阶段，新鉴定的分枝菌酸生物合成酶 将在一组同基因对菌株中进行检查， 从异烟肼敏感到异烟肼耐药， 治疗如果成功，这些研究应该提供新的信息， 关于药物作用和耐药性的机制，并提出新的 药物靶点在分枝菌酸代谢途径内。

DESCRIPTION (Adapted from the Applicant's Abstract): Tuberculosis has been classified as an emerging and re-emerging infectious disease. Contributing to its public health importance is the co-existing progression of the AIDS pandemic and the development of drug-resistant strains of Mycobacterium tuberculosis. This has lead to the recognition that more needs to be learned about essential metabolic pathways of the organism to provide a factual basis for the development of new antibiotics. This project addresses this question, proposing experiments designed to identify biosynthetic components of the metabolic pathway of mycolic acids, essential molecules of the M. tuberculosis cell wall. The research plan calls for the use of two new technologies of the "post-genomic era": use of the complete annotated M. tuberculosis genome and mRNA gene response profiling by microarray competitive hybridization. Microarray-based results will be complemented by biochemical and mutational studies performed in collaboration with Drs. Patrick Brennan and Brigitte Gicquel, respectively. In the terminal phase of this study, newly-identified mycolic acid biosynthetic enzymes will be examined in a group of isogenic pairs of strains which have evolved from isoniazid-sensitive to isoniazid-resistant during treatment. If successful, these studies should provide new information about mechanisms of drug-action and drug-resistance and suggest novel drug targets within the mycolic acid metabolic pathway.