Novel Reporter Phages to Detect Complex TB Drug Resistance and Persistence

描述（由申请人提供）：耐药结核病在南非引起的恐慌最大，在南非，地方性结核病和艾滋病毒之间的协同作用导致结核病发病率和病死率“爆炸性”增加。最耐药的结核病形式，广泛耐药结核病（XDR-TB），在南非日益流行。提高广泛耐药结核存活率的一个重要障碍是缺乏一种快速的生物标志物，用于识别活的结核分枝杆菌，允许在临床痰样本中进行药物敏感性测试并检测结核分枝杆菌。 顽固分子利用两种新的重组报告分枝杆菌噬菌体，我们已经开发出具有上级测试特性的检测方法，这将使我们能够表征复杂的耐药性和分枝杆菌在体内的持久性，以改善耐药性TB/HIV患者的治疗结果。这项建议是阿尔伯特·爱因斯坦医学院、夸祖鲁-纳塔尔结核病和艾滋病毒/艾滋病研究所（K-RITH）和桑格研究所的研究人员之间正在进行的资助合作的结果。这是一种创新方法，有可能对我们全面诊断耐药结核病和描述耐药结核病患者特征的能力产生重大影响，从而改善治疗结果，减少传播并防止治疗中耐药性的扩大。

DESCRIPTION (provided by applicant): Nowhere has drug-resistant TB generated more alarm than in South Africa, where synergies between endemic TB and HIV have caused 'explosive' increases in TB incidence and case- fatality rates. The most resistant form of TB, extensively drug resistant tuberculosis (XDR-TB), is increasingly prevalent in South Africa. An important obstacle to improving survival for XDR-TB is the lack of a rapid, biomarker that serves to identify viable Mtb, allow drug susceptibility testing in clinical sputum samples and detect Mtb persisters. Utilizing two novel recombinant reporter mycobacteriophages, we have developed assays with superior test characteristics that will allow us to characterize complex drug resistance and mycobacterial persistence in vivo to improve treatment outcomes for drug-resistant TB/HIV patients. This proposal is a result of an ongoing funded collaboration between researchers at Albert Einstein College of Medicine, the KwaZulu-Natal Research Institute for Research in Tuberculosis and HIV/AIDS (K-RITH), and the Sanger Institute. This is an innovative approach with the potential to make a substantial impact in our ability to comprehensively diagnose drug-resistant tuberculosis and characterize Mtb persister populations thereby improving treatment outcomes, reducing transmission and preventing amplification of drug resistance on treatment.