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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
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HSAF-induced antifungal effects in Candida albicans through ROS-mediated apoptosis

Yanjiao Ding1, Zhenyu Li1, Yaoyao Li1

  • 1Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, P. R. China.

RSC Advances
|September 6, 2016
PubMed

Insights

Heat-stable antifungal factor (HSAF) triggers fungal cell death in Candida albicans by increasing reactive oxygen species (ROS). This polycyclic tetramate macrolactam (PTM) shows promise as a novel antifungal agent in a mouse model.

Area of Science:

  • Mycology
  • Biochemistry
  • Pharmacology

Background:

  • Heat-stable antifungal factor (HSAF) is a polycyclic tetramate macrolactam (PTM) with known antifungal properties.
  • Candida albicans (C. albicans) is a significant fungal pathogen causing candidiasis.
  • Understanding the mechanism of HSAF action is crucial for developing new antifungal therapies.

Purpose of the Study:

  • To investigate the mechanism by which HSAF inhibits C. albicans.
  • To evaluate the in vivo efficacy of HSAF against candidiasis.
  • To elucidate the molecular interactions between HSAF and C. albicans.

Main Methods:

  • Induction of apoptosis in C. albicans SC5314 by HSAF.
  • Measurement of reactive oxygen species (ROS) production.
  • In vivo efficacy study in a murine model of candidiasis.
  • Molecular dynamics (MD) simulation of HSAF binding to C. albicans β-tubulin.

Main Results:

  • HSAF induced apoptosis in C. albicans through ROS accumulation.
  • HSAF significantly improved survival rates in a murine candidiasis model.
  • HSAF reduced fungal burden in vivo compared to control groups.
  • MD simulations revealed the binding mode of HSAF to C. albicans β-tubulin.

Conclusions:

  • PTMs, specifically HSAF, can induce fungal apoptosis via ROS accumulation in C. albicans.
  • HSAF demonstrates significant therapeutic potential as a novel antifungal agent for candidiasis.
  • The study provides a mechanistic and molecular basis for HSAF's antifungal activity.
Keywords:
Candida albicansHSAFapoptosisreactive oxygen species

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