Disulfiram, an alcohol dependence therapy, can inhibit the in vitro growth of Francisella tularensis
Disulfiram, an alcohol dependence therapy, can inhibit the in vitro growth of Francisella tularensis
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DOI：
10.1016/j.ijantimicag.2019.04.002
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发表时间：
2019-07-01
影响因子：
10.8
通讯作者：
Harding, Sarah V.
中科院分区：
文献类型：
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作者：
Hamblin, Karleigh A.;Flick-Smith, Helen;Harding, Sarah V.
双硫仑（DSF）可以通过抑制醛脱氢酶（ALDH）来帮助治疗酒精依赖。基因组分析显示，土拉菌（土拉菌病的病原体）失去了除一个aldh样结构域外的所有结构域，并且该结构域保留了DSF的靶标。最低抑菌浓度（MIC）测定表明，DSF及其主要代谢物二乙基二硫代氨基甲酸酯（DDC）对土拉菌SCHU S4具有较强的抑菌活性，DSF的MIC为2 μ g/mL，而DDC的MIC为8 μ g/mL。通过体外人巨噬细胞感染实验进一步证实了DSF的活性。与未处理和ddc处理的细胞相比，dsf处理的细胞中的土拉弗朗西斯菌细菌减少，与多西环素处理的细胞中观察到的情况相当。这表明DSF可能适合进一步研究作为兔热病的体内治疗方法。爱思唯尔B.V. 2019年版权所有
Disulfiram (DSF) can help treat alcohol dependency by inhibiting aldehyde dehydrogenase (ALDH). Genomic analysis revealed that Francisella tularensis, the causative agent of tularemia, has lost all but one ALDH-like domain and that this domain retains the target of DSF. In this study, minimum inhibitory concentration (MIC) assays demonstrated that both DSF and its primary metabolite diethyldithiocarbamate (DDC) have strong antimicrobial activity against F. tularensis strain SCHU S4, with the MIC of DSF determined as 2 mu g/mL in comparison with 8 mu g/mL for DDC. The activity of DSF was further confirmed using an in vitro human macrophage infection assay. Francisella tularensis bacteria in DSF-treated cells were reduced in comparison with untreated and DDC-treated cells, comparable with that observed in doxycycline-treated cells. This suggests that DSF may be suitable for further investigation as an in vivo therapy for tularemia. Crown Copyright (C) 2019 Published by Elsevier B.V.