Institute Pasteur Korea, Seongnam-si, Gyeonggi-do, Korea.
Department of Clinical Laboratory Science, Semyung University, Jecheon, Chungbuk, Korea.
J Antimicrob Chemother. 2014 Jun;69(6):1599-607. doi: 10.1093/jac/dku024. Epub 2014 Feb 10.
Mycobacterium abscessus is known to be the most drug-resistant Mycobacterium and accounts for ∼80% of pulmonary infections caused by rapidly growing mycobacteria. This study reports a new Drosophila melanogaster-M. abscessus infection model that can be used as an in vivo efficacy model for anti-M. abscessus drug potency assessment.
D. melanogaster were challenged with M. abscessus, and infected flies were fed with a fly medium containing tigecycline, clarithromycin, linezolid, clofazimine, moxifloxacin, amikacin, cefoxitin, dinitrobenzamide or metronidazole at different concentrations (0, 100 and 500 mg/L). The survival rates of infected flies were plotted and bacterial colonization/dissemination in fly bodies was monitored by cfu determination and green fluorescent protein epifluorescence.
The D. melanogaster-M. abscessus model enabled an assessment of the effectiveness of antibiotic treatment. Tigecycline was the best drug for extending the lifespan of M. abscessus-infected Drosophila, followed by clarithromycin and linezolid. Several different combinations of tigecycline, linezolid and clarithromycin were tested to determine the best combination. Tigecycline (25 mg/L) plus linezolid (500 mg/L) was the best drug combination and its efficacy was superior to conventional regimens, not only in prolonging infected fly survival but also against M. abscessus colonization and dissemination.
This D. melanogaster-M. abscessus infection/curing methodology may be useful for the rapid evaluation of potential drug candidates. In addition, new combinations using tigecycline and linezolid should be considered as possible next-generation combination therapies to be assessed in higher organisms.
脓肿分枝杆菌是已知耐药性最强的分枝杆菌，约占快速生长分枝杆菌引起的肺部感染的 80%。本研究报告了一种新的黑腹果蝇-脓肿分枝杆菌感染模型，可作为体内评估抗脓肿分枝杆菌药物效力的疗效模型。
用脓肿分枝杆菌感染黑腹果蝇，并用含有替加环素、克拉霉素、利奈唑胺、氯法齐明、莫西沙星、阿米卡星、头孢西丁、二硝基苯甲酰胺或甲硝唑的蝇培养基喂养感染的果蝇，浓度分别为 0、100 和 500mg/L。通过菌落形成单位（cfu）测定和绿色荧光蛋白荧光显微镜观察，绘制感染果蝇的存活率曲线，并监测蝇体内细菌定植/传播情况。
黑腹果蝇-脓肿分枝杆菌模型可用于评估抗生素治疗的效果。替加环素是延长脓肿分枝杆菌感染果蝇寿命的最佳药物，其次是克拉霉素和利奈唑胺。测试了几种替加环素、利奈唑胺和克拉霉素的不同组合，以确定最佳组合。替加环素（25mg/L）加利奈唑胺（500mg/L）是最佳药物组合，其疗效优于常规方案，不仅能延长感染果蝇的存活时间，而且能抑制脓肿分枝杆菌的定植和传播。
这种黑腹果蝇-脓肿分枝杆菌感染/治愈方法可能有助于快速评估潜在的候选药物。此外，应考虑使用替加环素和利奈唑胺的新组合作为可能的下一代联合治疗方案，在更高等的生物中进行评估。
