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Cryptococcus flips its lid - membrane phospholipid asymmetry modulates antifungal drug resistance and virulence

Erika Shor1, Yina Wang1, David S Perlin2

  • 1Public Health Research Institute Center, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.

Microbial Cell (Graz, Austria)
|March 31, 2017
PubMed

Insights

Infections from human fungi are rising, and drug resistance is growing. Researchers found that blocking lipid flippase, an enzyme in fungal cells, could make antifungal drugs more effective and reduce fungal infections.

Area of Science:

  • Mycology
  • Biochemistry
  • Drug Discovery

Background:

  • Rising prevalence of human fungal infections and increasing antifungal drug resistance pose a significant public health challenge.
  • Antifungal drugs often target the fungal cell membrane, but the role of membrane biology in drug interactions is poorly understood.
  • Phospholipid asymmetry is crucial for membrane function and is maintained by lipid transporters, including lipid flippases.

Purpose of the Study:

  • To investigate the role of lipid flippase in antifungal drug resistance and virulence in the pathogenic fungus *Cryptococcus neoformans*.
  • To explore lipid flippase as a potential novel target for antifungal drug development.

Main Methods:

  • Studied the effects of lipid flippase activity loss on *Cryptococcus neoformans*.
  • Assessed the sensitivity of *Cryptococcus neoformans* to various antifungal drugs.
  • Evaluated the impact of lipid flippase on fungal virulence in murine models.

Main Results:

  • Loss of lipid flippase activity resulted in abnormal phospholipid distribution and impaired vesicular trafficking in *Cryptococcus neoformans*.
  • Reduced lipid flippase activity sensitized cryptococcal cells to multiple classes of antifungal drugs, including echinocandins.
  • Abolished fungal virulence in murine models, indicating lipid flippase's role in pathogenesis.

Conclusions:

  • Lipid flippase activity contributes to antifungal drug resistance and virulence in *Cryptococcus neoformans*.
  • Inhibition of lipid flippase represents a promising strategy for developing new antifungal therapies.
  • Targeting lipid flippase could overcome existing drug resistance mechanisms in fungal infections.
Keywords:
Cdc50Cryptococcus neoformansantifungal drug resistancelipid flippasevirulence

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