Biochemical and regulatory mechanisms involved in secondary metabolism and antibiotic resistance in actinobacteria

放线菌次生代谢和抗生素耐药性涉及的生化和调节机制

• 批准号: 386417-2010
• 负责人: Tahlan, Kapil
• 金额: $ 2.4万
• 依托单位: Memorial University of Newfoundland
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2010
• 资助国家: 加拿大
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=463783
• 关键词: Biochemical; regulatory; mechanisms; involved; secondary

Infections caused by antibiotic resistant bacteria are a major problem, but the recent emergence and spread of bacterial diseases previously thought to be under control is cause for even greater concern. Clavulanic acid is a drug used in the treatment of infections caused by certain bacteria that are resistant to the penicillin family of antibiotics. When clavulanic acid is given in combination with a penicillin-type antibiotic, it restores the ability of the antibiotic to act against the targeted organism by silencing its resistance mechanism. Clavulanic acid is produced by Streptomyces clavuligerus, a bacterium that is related to a group of microorganisms (the Actinobacteria) that produce many medicinally important compounds. There is great interest in studying antibiotic production by the Actinobacteria with the aim of finding ways to improve antibiotic yields and to identify new molecules for novel applications. Industrial production of clavulanic acid for use in drug formulations is valued in excess of one billion dollars annually and my work will be crucial in determining how production takes place and how it is controlled in S. clavuligerus. I am interested in identifying key steps and regulatory mechanisms involved in the biosynthesis of clavulanic acid with the aim of improving its production. The long term goal of my research is to fully understand the biosynthesis and regulation of clavulanic acid so that the information gained can be applied more broadly to S. clavuligerus to produce new molecules for potential medicinal applications. My research program will contribute significantly to the training of students and other highly qualified personnel, which will benefit Canada by providing access to individuals skilled in the discovery of new natural products for targeting antibiotic resistant bacterial infections, in addition to other medicinal applications.

由抗生素抗性细菌引起的感染是一个主要问题，但是以前被认为受到控制的细菌疾病的最近出现和传播是引起更大关注的原因。克拉维烯酸是一种药物，用于治疗某些细菌引起的感染，这些细菌对青霉素抗生素的抗性药物具有抗性。当与青霉素型抗生素结合使用克拉夫拉酸时，它通过沉默的耐药机制来恢复抗生素对靶向生物的作用。克拉夫拉酸是由链霉菌链霉菌（Clavuligerus）产生的，克拉维利格素（Clavuligerus）与一组微生物（放线菌）相关的细菌产生，产生许多具有药物重要的化合物。在研究静脉细菌的抗生素生产方面非常感兴趣，目的是寻找改善抗生素产量并确定新应用的新分子的方法。克拉夫拉烯酸的工业生产用于药物配方的价值超过10亿美元，我的工作对于确定生产的发生方式以及如何在S. clavuligerus中进行控制至关重要。我有兴趣识别与克拉夫酸酸生物合成有关的关键步骤和调节机制，目的是改善其生产。我的研究的长期目标是充分了解克拉维烷酸的生物合成和调节，以便可以将获得的信息更广泛地应用于Clavuligerus，以生成用于潜在药用应用的新分子。我的研究计划将为学生和其他高素质的人员培训做出重大贡献，除其他药物应用外，还将通过提供熟练发现新天然产品来靶向抗生素耐药细菌感染的个人来使加拿大受益。