The biochemical characterisation of pivotal enzymes involved in mycobacterial peptidoglycan biosynthesis

分枝杆菌肽聚糖生物合成中涉及的关键酶的生化特征

• 批准号: G1001023/1
• 负责人: Gurdyal Besra
• 金额: $ 77.7万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1001023%2F1
• 关键词: biochemical; characterisation; pivotal; enzymes; involved

At least 30 million individuals worldwide will have died from tuberculosis (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 Mycobacterium tuberculosis strains that are resistant to virtually all the drugs that would normally be used to treat TB. It can be argued that, globally, M. tuberculosis 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, M. tuberculosis has a distinctive cell wall that differs in composition from that of other bacteria. Although there are drugs that affect the unique M. tuberculosis 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 M. tuberculosis. 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.

在20世纪的最后十年，全世界将至少有3000万人死于结核病。在英国，整个上个世纪结核病病例的稳步下降在20世纪80年代中期停止，并且在某些社区出现了令人担忧的病例数量增加的迹象。艾滋病的流行和结核分枝杆菌菌株的出现使情况更加复杂，结核分枝杆菌菌株对几乎所有通常用于治疗结核病的药物都具有耐药性。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。所有的细菌都有细胞，像植物一样，被包裹在细胞壁中。这保护了生物体免受其直接环境的影响，并偶然地为青霉素等可用于治疗细菌感染的药物提供了重要的靶标。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。虽然有一些药物可以影响独特的结核分枝杆菌细胞壁，但目前的结核病治疗持续6个月，对经常提前停止治疗的患者有潜在毒性。此外，治疗效果受到耐药结核分枝杆菌菌株出现的威胁。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明确的需要，以扩大我们对结核杆菌细菌生理学的理解，希望启动新的治疗方法来对付这个古老的人类对手。与公众的沟通将通过伯明翰大学新闻处（http://www.newscentre.bham.ac.uk/office.htm）进行，该办公室已与当地和全国媒体建立了联系。申请人还将通过个人大学网页强调他们的研究，这些网页是开放访问的。