Novel Reporter Phages to Detect Complex TB Drug Resistance and Persistence

用于检测复杂结核病耐药性和持久性的新型报告噬菌体

• 批准号: 9060871
• 负责人: Michelle H Larsen
• 金额: $ 65.05万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9060871
• 关键词: AIDS/HIV problem; Acid Fast Bacillae Staining Method; Admission activity; Antibiotic Therapy; Antibiotics; Bacillus (bacterium); Bacteriophages; Biological Assay; Biological Markers; Case Fatality Rates; Cells; Characteristics; Clinical; Clinical Data; Collaborations; Communities; Complex; Diagnosis; Diagnostic; Drug resistance; Drug resistance in tuberculosis; England; Epidemic; Extreme drug resistant tuberculosis; Funding; Genes; Genetic; HIV; HIV/TB; Hospital Referrals; Human; Incidence; Infection; Institutes; Laboratories; Measures; Medicine; Metabolic; Multidrug-Resistant Tuberculosis; Mycobacteriophages; Mycobacterium tuberculosis; Newly Diagnosed; Pathway interactions; Patients; Pharmaceutical Preparations; Plasmids; Population; Predisposition; Prevalence; Prevention; Public Health; Recombinants; Regimen; Reporter; Research; Research Institute; Research Personnel; Resistance; Rifampicin resistance; Role; Sampling; Scientist; South Africa; Sputum; Testing; Treatment Failure; Treatment outcome; Tuberculosis; Work; base; chemotherapy; college; extensive drug resistance; improved; in vivo; in vivo Model; innovation; killings; molecular diagnostics; mycobacterial; novel; prevent; promoter; public health relevance; research facility; research study; resistant strain; success; transcriptomics; transmission process; treatment duration; tuberculosis treatment

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.

描述（由申请人提供）：与南非相比，耐药结核病的任何地方都没有更多的警报，在南非，地方性结核病和艾滋病毒之间的协同作用导致了结核病发生率和病例死亡率的“爆炸性”增加。在南非，结核病（XDR-TB）广泛的抗药性结核病（XDR-TB）的最具耐药性形式在南非越来越普遍。改善XDR-TB生存的重要障碍是缺乏快速的生物标志物，该标志物可识别可行的MTB，允许在临床痰样品中进行药物敏感性测试并检测MTB 毅力。利用两种新型的重组记者分枝杆菌噬菌体，我们开发了具有较高测试特征的测定法，这将使我们能够表征体内复杂的耐药性和分生不清的耐分菌性，以改善耐药性结核病/HIV患者的治疗结果。该提案是阿尔伯特·爱因斯坦医学院，夸祖鲁 - 纳塔尔邦研究研究所的研究人员与艾滋病毒和艾滋病毒/艾滋病研究所（K-RITH）和桑格研究所之间持续资助的合作的结果。这是一种创新的方法，有可能对我们全面诊断抗药性结核病并表征MTB持久种群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时耐药性的扩增。