Novel drug combination for Mycobacterium abscessus disease therapy identified in a Drosophila infection model
Novel drug combination for Mycobacterium abscessus disease therapy identified in a Drosophila infection model
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DOI：
10.1093/jac/dku024
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发表时间：
2014-06-01
影响因子：
5.2
通讯作者：
Jang, Jichan
中科院分区：
文献类型：
--
作者：
Oh, Chun-Taek;Moon, Cheol;Jang, Jichan
已知分枝杆菌是最耐药的分枝杆菌，并且占由快速生长的分枝杆菌引起的肺部感染的80%。本文报道了一种新的果蝇属果蝇M.可用作抗M.药物效力评价。用M.用含有不同浓度（0、100和500 mg/L）的替加环素、克拉霉素、利奈唑胺、氯法齐明、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。以存活率为指标，以菌落形成单位数（cfu）和绿色荧光蛋白（GFP）为荧光标记物，监测感染后蝇体内细菌的定植和传播情况。黑腹鼠M.该模型能够评估抗生素治疗的有效性。替加环素是延长M.感染果蝇，其次是克拉霉素和利奈唑胺。检测了替加环素、利奈唑胺和克拉霉素的几种不同组合，以确定最佳组合。替加环素（25 mg/L）+利奈唑胺（500 mg/L）是最佳药物组合，其疗效上级优于常规方案，不仅在延长感染蝇存活方面，而且在抗M.这种D.黑腹鼠M.感染/治愈方法可能有助于快速评价潜在的候选药物。此外，使用替加环素和利奈唑胺的新组合应被视为可能的下一代组合疗法，以在高等生物中进行评估。
Mycobacterium abscessus is known to be the most drug-resistant Mycobacterium and accounts for similar to 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.