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Sphaeropsidin A Loaded in Liposomes to Reduce Its Cytotoxicity and Preserve Antifungal Activity Against Candida auris

Annalisa Buonanno1, Maria Michela Salvatore1,2, Antonia Feola1

  • 1Department of Biology, University of Naples Federico II, Via Cinthia, 80126 Naples, Italy.

Molecules (Basel, Switzerland)
|January 8, 2025
PubMed

Insights

Sphaeropsidin A (SphA) and its liposomal form (SphA-L) show potent antifungal activity against Candida auris, inhibiting biofilm formation and reducing fungal load in infection models. This discovery offers a promising new therapeutic avenue for combating drug-resistant fungal infections.

Area of Science:

  • Mycology
  • Pharmacology
  • Infectious Diseases

Background:

  • Candida species are common causes of human fungal infections, with resistance and biofilm formation posing significant challenges.
  • Candida auris outbreaks are increasing globally, causing superficial to life-threatening disseminated infections.
  • Mechanisms of drug resistance and biofilm formation in C. auris are poorly understood, necessitating new therapeutic strategies.

Purpose of the Study:

  • To investigate the antifungal properties of Sphaeropsidin A (SphA), a metabolite from Diplodia fungi, against Candida auris.
  • To evaluate the efficacy of SphA and its liposomal form (SphA-L) in inhibiting C. auris growth and biofilm formation.
  • To elucidate the mechanism of action of SphA against C. auris.

Main Methods:

  • Time-kill kinetics assays were used to determine the fungistatic and fungicidal activity of SphA and SphA-L.
  • Biofilm formation inhibition assays were conducted to assess the impact of SphA and SphA-L on C. auris biofilms.
  • Studies on reactive oxygen species (ROS) production and cell cycle disruption were performed to understand the antifungal mechanism.
  • Adherence assays using human epithelial cell lines and Caenorhabditis elegans infection models were employed to evaluate SphA-L's efficacy and safety.

Main Results:

  • SphA and SphA-L demonstrated fungistatic activity with significant inhibition of Candida auris biofilm formation.
  • Antifungal mechanisms involved alterations in ROS production and disruption of the Candida cell cycle.
  • SphA-L effectively impaired C. auris adherence to human epithelial cells without causing harm to the cells.
  • In vivo studies using C. elegans models showed reduced fungal load and improved survival rates with SphA and SphA-L treatment.

Conclusions:

  • SphA and SphA-L exhibit potent antifungal effects against Candida auris, including inhibition of biofilm formation and key pathogenic traits.
  • The observed mechanisms involve ROS modulation and cell cycle disruption, highlighting SphA-L's potential as a therapeutic agent.
  • SphA-L demonstrates safety towards human cells and efficacy in infection models, warranting further research for clinical application.
Keywords:
Caenorhabditis elegansCandida aurisROS productionSphaeropsidin Aantifungal activitybiofilmloaded liposomenosocomial infection

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