MTB--MYCOLIC ACID BIOSYNTHETIC AND REGULATORY GENES

描述(改编自申请者摘要)：结核病 被归类为新发和再次出现的传染病。 其公共卫生重要性的贡献是共存的 艾滋病大流行的进展与耐药性的发展 结核分枝杆菌菌株。这导致了人们对 我们需要更多地了解心脏的基本代谢途径。 有机体为新的发展提供事实基础 抗生素。这个项目解决了这个问题，提出了实验方案。 用于识别代谢途径的生物合成成分 分枝菌酸，结核分枝杆菌细胞壁的基本分子。 这项研究计划要求使用两项新技术 “后基因组时代”：使用完整的结核分枝杆菌注释基因组 基因芯片竞争性检测基因反应谱 杂交。基于微阵列的结果将得到以下补充 生化和突变研究是与戴维斯博士合作进行的。 分别是帕特里克·布伦南和布里吉特·吉克尔。在航站楼 本研究阶段，新鉴定的霉酚酸生物合成酶 将在一组具有相同基因对的菌株中进行检测 从对异烟肼敏感进化到对异烟肼耐药 治疗。如果成功，这些研究应该会提供新的信息 关于药物作用和耐药机制的探讨及建议 霉菌酸代谢途径中的药物靶点。

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.