Galleria mellonella: a novel infection model for screening potential anti-mycobacterial compounds against members of the Mycobacterium tuberculosis complex
Galleria mellonella: a novel infection model for screening potential anti-mycobacterial compounds against members of the Mycobacterium tuberculosis complex
复制标题
大蜡螟：一种新型感染模型，用于筛选针对结核分枝杆菌复合体成员的潜在抗分枝杆菌化合物
DOI：
10.1099/acmi.ac2019.po0172
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发表时间：
2019
影响因子：
--
通讯作者：
Asai M
中科院分区：
文献类型：
--
作者：
Asai M
动物感染模型作为应对全球结核病(TB)流行的新疗法的药物筛选至关重要。然而，所有先前存在的模型都有局限性，其中包括道德约束。因此，在结核病研究中减少和/或取代传统动物模型的努力是必要的。此前，我们报道了使用Galeria mellonella(大蜡蛾，GM)作为结核分枝杆菌(MTB)复合体的一种新的感染模型，使用BCG lux，一种生物发光突变体，允许快速定量体内的细菌负荷。在这里，我们研究了感染致死剂量的卡介苗勒克斯，在96 h内用一线或二线抗分枝杆菌药物治疗的GM的药物筛选潜力；其中通过对幼虫匀浆的生物发光测量每24 h确定一次药物疗效。与未处理的对照相比，使用抗分枝杆菌药物的所有幼虫的存活结果都得到了改善。此外，除吡津酰胺外，所有药物处理均导致卡介苗Luxin体内的生物发光显著降低。异烟肼和利福平显示出最高的存活结果和伟大的活体药物疗效，与在小鼠中的观察结果一致。然而，联合或多次服用这两种药物与单一剂量的治疗相比，差异很小或没有差异。我们的结果表明，对于结核分枝杆菌复合体的成员来说，GM是一个很有前途的感染模型，它在药物开发流水线中作为新疗法的预筛选模型具有巨大的潜力，从而减少了动物在结核病研究中的实验使用。由NC3R支持(NC/R001596/1)
Animal infection models are vital as drug screens for novel therapeutics to tackle the global tuberculosis (TB) epidemic. However, all pre-existing models have limitations which include ethical constraints. Therefore, efforts to reduce and/or replace conventional animal models in TB research are warranted. Previously, we reported the use ofGalleria mellonella(greater wax moth, GM) as a novel infection model for theMycobacterium tuberculosis(MTB) complex, usingMycobacterium bovisBCG lux, a bioluminescent mutant which allows for the rapid quantification of bacterial burdenin vivo. Here we investigated the drug screening potential of GM infected with a lethal dose of BCG lux, treated with first or second-line antimycobacterial drugs over a 96 h period; where drug efficacy was determined every 24 h through bioluminescent measurement of larval homogenates. Improved survival outcome was observed in all larvae treated with antimycobacterials when compared to untreated controls. Furthermore, all drug treatments except pyrazinamide resulted in a significant reduction in bioluminescence of BCG luxin vivo. Isoniazid and rifampicin displayed the highest survival outcome and greatestin vivodrug efficacy, in line with observations reported in mice. However, combined or multiple dosing of either drug showed little to no difference over single dose mono-therapy. Our results demonstrate that GM is a promising infection model for members of the MTB complex, with significant potential for its use in the drug development pipeline as a pre-screening model for novel therapeutics, thereby reducing experimental usage of animals in TB research. Supported by the NC3R’s (NC/R001596/1)