Fingolimod Potentiates the Antifungal Activity of Amphotericin B.
Fingolimod Potentiates the Antifungal Activity of Amphotericin B.
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芬戈莫德增强两性霉素 B 的抗真菌活性。
DOI：
10.3389/fcimb.2021.627917
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发表时间：
2021
影响因子：
5.7
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Wei LQ;Tan JC;Wang Y;Mei YK;Xue JY;Tian L;Song KY;Han L;Cui YC;Peng YB;Li JQ;Liu NN;Wang H
白色念珠菌（C.白色念珠菌（albicans）是一种机会致病真菌，临床上可引起严重感染。其发病率和死亡率一直在迅速上升。两性霉素B（AMB）作为临床抗真菌药物的金标准，其严重的毒副作用限制了其临床应用。因此，降低浓度和提高AMB在组合抗真菌治疗中的功效一直是工业界和学术界所追求的。在这里，我们确定了芬戈莫德（FTY 720），一种用于复发缓解型多发性硬化症口服治疗的免疫调节药物，可以增强AMB对C。白色念珠菌生长协同作用。此外，我们观察FTY 720与AMB组合对多种真菌病原体的抗真菌功效。有趣的是，用这两种药物治疗的细胞对内皮细胞内吞和巨噬细胞杀伤都非常敏感。后来发现，这是由于活性氧的过度积累和相应的增加超氧化物歧化酶和过氧化氢酶的活性在细胞中接受组合治疗。因此，AMB和FTY 720的组合提供了一种有希望的抗真菌策略。
Candida albicans (C. albicans) is an opportunistic human fungal pathogen that can cause severe infection in clinic. Its incidence and mortality rate has been increasing rapidly. Amphotericin B (AMB), the clinical golden standard antifungal agent, has severe side effects that limit its clinical application. Thus, lowering the concentration and increasing the efficacy of AMB in a combinatorial antifungal therapy have been pursued by both industry and academia. Here we identify that fingolimod (FTY720), an immunomodulatory drug used for oral treatment of relapsing-remitting multiple sclerosis, can potentiate the efficacy of AMB against C. albicans growth synergistically. Furthermore, we observe an antifungal efficacy of FTY720 in combination with AMB against diverse fungal pathogens. Intriguingly, cells treated with both drugs are hypersensitive to endothelial endocytosis and macrophage killing. This is later found to be due to the hyperaccumulation of reactive oxygen species and the corresponding increase in activities of superoxide dismutase and catalase in the cells that received combinatorial treatment. Therefore, the combination of AMB and FTY720 provides a promising antifungal strategy.
影响因子：
11.8
作者：
Goosney, D L;Knoechel, D G;Finlay, B B
通讯作者：
Finlay, B B