Ferrous sulfate induces ferroptosis-like cell death in Trichosporon asahii

Lingzhi Xu1,2, Haochen Guo1,2, Xin Yang2

  • 1Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.

Insights

Ferrous sulfate (FeSO₄) effectively inhibits Trichosporon asahii by inducing ferroptosis-like cell death. This novel mechanism involves iron accumulation and lipid peroxidation, offering a new avenue for antifungal drug development.

Area of Science:

  • Mycology
  • Pathogen Research
  • Cell Death Mechanisms

Background:

  • Trichosporon asahii is a major cause of invasive fungal infections.
  • This pathogen shows resistance to common antifungal drugs, complicating treatment.

Purpose of the Study:

  • To investigate the antifungal effects of ferrous sulfate (FeSO₄) against Trichosporon asahii.
  • To elucidate the cell death pathway induced by FeSO₄ in this fungus.

Main Methods:

  • Treatment of Trichosporon asahii with ferrous sulfate (FeSO₄).
  • Analysis of cell death characteristics including apoptosis, iron dependence, reactive oxygen species (ROS), and lipid peroxidation.
  • Assessment of mitochondrial membrane potential.
  • Reversal studies using the ferroptosis inhibitor Ferrostatin-1.
  • Transcriptomic analysis to identify affected gene pathways.

Main Results:

  • FeSO₄ demonstrated potent inhibition of Trichosporon asahii.
  • FeSO₄ induced a ferroptosis-like cell death, characterized by non-apoptotic death, iron dependence, ROS burst, and lipid peroxidation.
  • Mitochondrial membrane potential was damaged.
  • Ferrostatin-1 partially reversed the cell death, confirming ferroptosis involvement.
  • Transcriptomic analysis revealed alterations in redox, glutathione metabolism, and proteasome pathways.

Conclusions:

  • Ferrous sulfate triggers a novel ferroptosis-like death pathway in Trichosporon asahii.
  • This pathway is dependent on iron accumulation and lipid peroxidation.
  • This discovery presents a new ferroptosis-based strategy for developing antifungal therapies against resistant fungi.

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