# Otilonium bromide exhibits novel antifungal activity against Candida albicans via regulating iron homeostasis

## TL;DR

Otilonium bromide, a drug used for irritable bowel syndrome, shows antifungal activity against Candida albicans by affecting iron balance and cell membrane integrity.

## Contribution

The novel antifungal activity of otilonium bromide against C. albicans via iron homeostasis regulation is reported.

## Key findings

- Otilonium bromide inhibits C. albicans at 2 μg/mL by damaging cell membranes and preventing yeast-to-hyphae transition.
- Iron ions negate the antifungal effect of otilonium bromide, indicating a role for iron homeostasis in its mechanism.
- Otilonium bromide showed limited efficacy in reducing C. albicans in a murine infection model.

## Abstract

Traditional antifungal drugs used against Candida albicans have several drawbacks, including the emergence of drug-resistant strains. In addition, developing novel antifungal agents requires long-term research and design. Drug repurposing, identifying and utilizing previously unknown functions of known drugs, such as antifungal activity, may be a quick method for mining efficient alternatives. Otilonium bromide (OB), an FDA-approved drug, is a quaternary ammonium compound used as a therapeutic drug for irritable bowel syndrome. We previously reported the inhibitory effect of OB against the spore germination of Cryptococcus neoformans. In this study, we found that the antifungal activity of OB against C. albicans was 2 μg/mL for both minimum inhibitory and fungicidal concentrations. OB could destroy the cell membrane and prevent C. albicans from undergoing yeast-to-hyphae transition, thus interfering with biofilm formation. Additionally, the efficacy of OB was abolished when iron ions were provided, suggesting that iron homeostasis was associated with the inhibition mechanism of OB. Interestingly, a therapeutic assay showed that OB demonstrated limited efficacy in reducing C. albicans burden in a murine systemic infection model. In summary, repurposing OB against C. albicans may facilitate the design of new antifungal drugs, and chemical modification could enhance the efficacy of OB to be more specific to fungal pathogens.