Newton001 Understanding Antimicrobial Resistance Mutations in Tuberculosis: Towards Personalised Treatment to Combat Multi-drug Resistance

结核病被认为是巴西的主要传染病之一，每年报告的病例超过7万例。确诊的耐多药结核病病例大幅增加，其中10%的人也对两种最重要的二线药物(XDR-TB)耐药。该项目旨在建立在现有合作项目的基础上，了解突变的影响，以及抗击多重耐药和广泛耐药(分别为MDR和XDR)结核病(TB)。巴西和英国这两个节点拥有互补的技能，涵盖流行病学、人类和病原体遗传学、生物信息学、结构生物学和药物发现。这种多学科的结合将有助于开发一种新的平台，从基因组测序中快速识别耐药结核病。将利用尖端技术探索结核病耐药的新机制，并与临床结果相关联。这将有助于指导更合适的患者治疗、公共卫生政策和未来的药物发现努力，有可能为巴西和英国的个人和公共卫生带来好处，为影响世界三分之一人口的问题提供解决方案。

Tuberculosis is recognised as one of Brazil's leading infectious diseases, with over 70,000 cases notified each year. There has been a significant increase in the number of diagnosed Multidrug resistant TB cases, with 10% of those also resistant to the two most important second---line class drugs (XDR-TB). This project aims to build upon existing collaborative programs on understanding effects of mutations, and on combating multidrug resistant and extensively drug resistant (MDR and XDR respectively) tuberculosis (TB). The two nodes, Brazil and UK, have complementary skills that encompass epidemiology, human and pathogen genetics, bioinformatics, structural biology and drug discovery. This multidisciplinary combination will facilitate the development of a novel platform to rapidly identify resistant TB from genomic sequencing. Novel mechanisms of drug resistance in TB will be explored using cutting edge techniques and correlated with clinical outcomes. This will help guide more suitable patient treatment, public health policies and future drug discovery efforts, with potential to bring benefit to individuals and public health in Brazil and UK, providing solutions to a problem that affects a third of the world's population.