Biochemical characterisation of pivotal enzymes involved in mycobacterial mycolic acid biosynthesis

结核病(TB)是一种威胁生命的疾病，可持续数年，在此期间患者虚弱，并可能传播导致疾病的细菌--结核分枝杆菌(Mtb)。在20世纪的最后十年里，全世界将至少有3000万人死于结核病。在英国，上个世纪整个结核病病例的稳步下降在1980年代中期停止，某些社区的病例数量出现了令人震惊的增加迹象。艾滋病的流行以及对通常用于治疗结核病的几乎所有药物都具有抗药性的结核分枝杆菌菌株的出现，使这种情况更加复杂。可以说，在全球范围内，结核分枝杆菌是影响人类的最重要的单一传染病病原体。所有细菌都有像植物一样被包裹在细胞壁中的细胞。这保护了有机体免受其直接环境的影响，幸运的是，它为青霉素等可用于治疗细菌感染的药物提供了一个重要的靶点。然而，结核分枝杆菌有一个独特的细胞壁，在组成上与其他细菌不同；特别是它含有大量独特的脂类(脂肪)和糖。尽管有一些药物会影响独特的结核分枝杆菌细胞壁，但目前对结核病的治疗持续6个月，对经常提前停止治疗的患者具有潜在的毒性。此外，结核分枝杆菌耐药株的出现威胁到了治疗的有效性。非常需要新的、更好的药物来治疗结核病。因此，这里提出的工作显然满足了我们对结核杆菌的细菌生理学的理解的需要，希望为这个古老的人类对手提供新的治疗方法。将通过设在伯明翰的大学新闻办公室(http://www.newscentre.bham.ac.uk/office.htm))向公众进行宣传，该办公室已与当地和国家媒体建立了联系。申请者还将通过开放访问的基于个人大学的网页突出这些研究。

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.