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Otilonium Bromide Exhibits Potent Antifungal Effects by Blocking Ergosterol Plasma Membrane Localization and

Cheng Zhen1, Li Wang1, Yanru Feng1

  • 1Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No.1239 Siping Road, Shanghai, 200092, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|July 12, 2024
PubMed

Insights

Otilonium bromide shows promise as a novel antifungal drug. It disrupts fungal cell membranes and induces self-destruction, offering a new strategy against Candida infections resistant to azoles.

Area of Science:

  • Mycology
  • Pharmacology
  • Biochemistry

Background:

  • Candidiasis poses a significant health risk, with azole antifungals facing challenges from drug interactions and emerging resistance.
  • Inhibiting the human CYP3A4 enzyme by azoles leads to drug-drug interactions, necessitating alternative antifungal treatments.

Purpose of the Study:

  • To identify novel antifungal agents through drug repurposing.
  • To investigate otilonium bromide (OTB) as a potential therapeutic for candidiasis.

Main Methods:

  • A drug repurposing screen of FDA-approved drugs was conducted.
  • The antifungal mechanism of OTB was elucidated, focusing on its effects on vesicle-mediated trafficking and ergosterol transport.

Main Results:

  • Otilonium bromide (OTB) was identified as a potent antifungal agent.
  • OTB disrupts ergosterol transport by targeting Sec31, impairing plasma membrane localization of transporters.
  • OTB induces cytotoxic autophagy and is not subject to efflux pump-mediated resistance in Candida species.

Conclusions:

  • OTB presents a novel antifungal mechanism by disrupting ergosterol homeostasis and inducing autophagy.
  • OTB circumvents azole-associated hepatotoxicity and drug resistance issues, offering a promising alternative for candidiasis treatment.
Keywords:
autophagycandida albicansergosterol plasma membrane localizationotilonium bromide

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