Fingolimod Potentiates the Antifungal Activity of Amphotericin B

Frontiers in Cellular and Infection Microbiology

Ying-Chao Cui¹  Yi-Bing Peng²  Jing-Cong Tan³  Lei Tian³  Ning-Ning Liu³  Jia-Yu Xue³  Ke-Yu Song³  Yi-Kun Mei³  Jing-Quan Li³  Lu Han³  Yue Wang³  Hui Wang³  Lu-Qi Wei³ 

[1] Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Faculty of Medical Laboratory Science, Shanghai Jiao Tong University School of Medicine, Shanghai, China;State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China;

关键词: Candida albicans (C. albicans);    antifungal agents;    amphotericin B (AMB);    fingolimod (FTY720);    reactive oxygen species (ROS);   

DOI  :  10.3389/fcimb.2021.627917

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY