Otilonium bromide unexpectedly acts as an antifungal agent by blocking ergosterol membrane localization

In this study, a drug repositioning strategy was used to perform high-throughput screening of a library consisting of United States Food and Drug Administration (FDA)-approved compounds. Through this screening process, otilonium bromide (OTB) was identified as a potent antifungal agent, exhibiting a low minimum inhibitory concentration (MIC) value, a wide range of antifungal activity, and minimal cytotoxic effects. Interestingly, in further studies of the antifungal mechanism of OTB we found that although the antifungal activity of OTB is reliant on the impairment of ergosterol function, it does not function as an ergosterol inhibitor; rather, it impedes the transportation of ergosterol between membranes.