Immunomodulatory drug fingolimod (FTY720) restricts the growth of opportunistic yeast Candida albicans in vitro and in a mouse candidiasis model

Abstract

Fingolimod (FTY720) is a drug derived from the fungicidal compound myriocin. As it was unclear whether FTY720 has antifungal effects as well, we aimed to characterize its effect on Candida albicans in vitro and in a mouse candidiasis model. First, antifungal susceptibility testing was performed in vitro. Then, a randomized, six-arm, parallel, open-label trial was conducted on 48 mice receiving oral FTY720 (0.3 mg/kg/day), intraperitoneal C. albicans inoculation, or placebo with different combinations and chorological patterns. The outcome measures of the trial included serum concentrations of interleukin-10 and interferon-gamma, absolute lymphocyte counts, and fungal burden values in the mice’s livers, kidneys, and vaginas. Broth microdilution assay revealed FTY720’s minimum inhibitory concentration (MIC99) to be 0.25 mg/mL for C. albicans. The infected mice treated with FTY720 showed lower fungal burden values than the ones not treated with FTY720 (p<0.05). As expected, the mice treated with FTY720 showed a less-inflammatory immune profile compared to the ones not treated with FTY720. We hypothesize that FTY720 synergizes the host’s innate immune functions by inducing the production of reactive oxygen species. Further studies are warranted to unveil the mechanistic explanations of our observations and clarify further aspects of repurposing FTY720 for clinical antifungal usage.