Metformin as adjunct antituberculosis therapy
Metformin as adjunct antituberculosis therapy
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DOI：
10.1126/scitranslmed.3009885
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发表时间：
2014-11-19
影响因子：
17.1
通讯作者：
De Libero, Gennaro
中科院分区：
文献类型：
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作者：
Singhal, Amit;Jie, Liu;De Libero, Gennaro
结核病（TB）发病率和死亡率的全球负担仍然巨大。结核病治疗的一种潜在新方法是增强宿主的保护性免疫反应。我们报道抗糖尿病药物二甲双胍 (MET) 以 AMPK（腺苷单磷酸激活蛋白激酶）依赖性方式减少结核分枝杆菌 (Mtb) 的细胞内生长。 MET 控制耐药 Mtb 菌株的生长，增加线粒体活性氧的产生，并促进吞噬体-溶酶体融合。在感染 Mtb 的小鼠中，使用 MET 可以改善肺部病理，减少慢性炎症，并增强特异性免疫反应和传统结核病药物的疗效。此外，在两个独立的人类队列中，MET 治疗与改善 Mtb 感染控制和降低疾病严重程度相关。总的来说，这些数据表明 MET 是一种有前途的候选宿主辅助疗法，可提高结核病的有效治疗效果。
The global burden of tuberculosis (TB) morbidity and mortality remains immense. A potential new approach to TB therapy is to augment protective host immune responses. We report that the antidiabetic drug metformin (MET) reduces the intracellular growth of Mycobacterium tuberculosis (Mtb) in an AMPK (adenosine monophosphate-activated protein kinase)-dependent manner. MET controls the growth of drug-resistant Mtb strains, increases production of mitochondrial reactive oxygen species, and facilitates phagosome-lysosome fusion. In Mtb-infected mice, use of MET ameliorated lung pathology, reduced chronic inflammation, and enhanced the specific immune response and the efficacy of conventional TB drugs. Moreover, in two separate human cohorts, MET treatment was associated with improved control of Mtb infection and decreased disease severity. Collectively, these data indicate that MET is a promising candidate host-adjunctive therapy for improving the effective treatment of TB.