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Updated: Jan 8, 2026
A Soluble Tetrazolium-Based Reduction Assay to Evaluate the Effect of Antibodies on Candida tropicalis Biofilms
Published on: September 16, 2022
Otilonium bromide exhibits novel antifungal activity against Candida albicans via regulating iron homeostasis
Li-Hang Hsu1, Yuk-Ping Chou1, Tang-Long Shen1
1Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan.
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.
Insights
Otilonium bromide (OB) shows antifungal activity against Candida albicans by disrupting cell membranes and inhibiting biofilm formation. Further research and chemical modification are needed to enhance its efficacy for treating fungal infections.
Area of Science:
- Mycology
- Pharmacology
- Drug Discovery
Background:
- Traditional antifungal drugs face challenges like resistance and slow development of new agents.
- Drug repurposing offers a faster approach to identify novel antifungal therapies.
- Otilonium bromide (OB), an FDA-approved drug for irritable bowel syndrome, has shown prior antifungal potential.
Purpose of the Study:
- To investigate the antifungal activity of Otilonium bromide (OB) against Candida albicans.
- To elucidate the mechanism of action of OB against C. albicans.
- To evaluate the therapeutic efficacy of OB in a preclinical model.
Main Methods:
- Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) assays.
- Cell membrane integrity assays and yeast-to-hyphae transition inhibition studies.
- Biofilm formation assays and iron ion interaction studies.
- In vivo efficacy assessment in a murine systemic infection model.
Main Results:
- OB exhibited potent antifungal activity against C. albicans with MIC and MFC of 2 μg/mL.
- OB disrupted the cell membrane, prevented yeast-to-hyphae transition, and inhibited biofilm formation.
- The antifungal effect of OB was reversed by iron ions, indicating a role for iron homeostasis.
- OB showed limited efficacy in a murine model of systemic C. albicans infection.
Conclusions:
- Repurposing OB presents a viable strategy for developing new antifungal drugs against C. albicans.
- Chemical modification of OB may be necessary to improve its specificity and efficacy for fungal pathogens.
- Understanding OB's interaction with iron homeostasis could guide future antifungal drug design.
