Biochemical characterisation of pivotal enzymes involved in mycobacterial mycolic acid biosynthesis

肺结核（TB）是一种生命吗？一种可持续数年的威胁性疾病，患者在此期间身体虚弱，并可能传播导致疾病的细菌，结核分枝杆菌（Mtb）。在20世纪的最后十年，全世界至少有3000万人死于结核病。在英国，结核病病例在整个上个世纪的稳步下降在20世纪80年代中期停止了，并且在某些社区出现了病例数量增加的惊人迹象。艾滋病的流行和结核分枝杆菌菌株的出现使这种情况更加复杂，这些菌株对通常用于治疗结核病的几乎所有药物都有抗药性。可以说，在全球范围内，结核分枝杆菌是影响人类的单一最重要的传染源。所有的细菌都有像植物一样被包围在细胞壁中的细胞。这保护了生物体免受其直接环境的影响，并且偶然地为药物提供了一个重要的靶点，如青霉素，可用于治疗细菌感染。然而，结核分枝杆菌具有独特的细胞壁，其组成与其他细菌不同;特别是它含有大量独特的脂质（脂肪）和糖。虽然有药物可以影响独特的结核杆菌细胞壁，但目前结核病的治疗持续6个月，对经常提前停止治疗的患者有潜在毒性。此外，结核分枝杆菌耐药菌株的出现威胁到治疗的功效。迫切需要新的和更好的药物来治疗结核病。因此，这里提出的工作满足了扩展我们对结核杆菌的细菌生理学的理解的明确需要，希望为这个古老的人类对手提供新的治疗方法。将通过伯明翰大学新闻处（http：//www.newscentre.bham.ac.uk/office.htm）向公众进行宣传，该新闻处已与地方和国家媒体建立了联系。申请人还将通过基于个人大学的网页突出研究，该网页具有开放访问权限。

Tuberculosis (TB) is a life?threatening condition that can last for several years during which patients are debilitated and may disseminate the bacterium that causes the disease, Mycobacterium tuberculosis (Mtb). At least 30 million individuals worldwide will have died from TB in the last decade of the 20th century. In the UK the steady decline in TB cases over the whole of the last century halted in the mid 1980s and there has been alarming signs of increased numbers of cases in certain communities. The situation is compounded by the AIDS epidemic and by the emergence of Mtb strains that are resistant to virtually all the drugs that would normally be used to treat TB. It can be argued that, globally, Mtb is the single most important infectious agent affecting mankind. All bacteria have cells that, like plants, are enclosed in a cell wall. This protects the organism from its immediate environment and, fortuitously, presents an important target for drugs, like penicillin, that can be used to treat bacterial infections. However, Mtb has a distinctive cell wall that differs in composition from that of other bacteria; in particular it contains an exceptional amount of unique lipids (fats) and sugars. Although there are drugs that affect the unique Mtb cell wall, the current treatment for tuberculosis lasts 6 months and is potentially toxic to patients who often cease treatment early. Moreover, the efficacy of treatment is threatened by the emergence of drug-resistant strains of Mtb. There is a great need for new and better drugs to treat TB. The work proposed here therefore fulfils the clear need to extend our understanding of the bacterial physiology of the tubercle bacillus in the hope of priming novel therapeutic approaches to this ancient human adversary. Communication to the general public will be channelled through the University Press Office at Birmingham (http://www.newscentre.bham.ac.uk/office.htm) which has established contacts in the local and national media. The applicants will also highlight there research through personal University based Web pages, which has open access.