Plasma membrane architecture protects Candida albicans from killing by copper

Area of Science:

• Mycology
• Cell Biology
• Pathogen Resistance

Background:

• Copper toxicity is a key defense mechanism used by innate immune cells against microbial pathogens.
• The fungal pathogen Candida albicans requires copper resistance for virulence and survival.
• The Sur7 protein, located in plasma membrane MCC/eisosomes, is crucial for copper resistance in Candida albicans.

Purpose of the Study:

• To investigate the role of Sur7 and MCC/eisosomes in copper resistance in Candida albicans.
• To identify new genetic factors contributing to copper sensitivity in fungal pathogens.
• To elucidate the mechanisms by which plasma membrane integrity influences copper toxicity.

Main Methods:

• Genetic screening to identify copper-sensitive mutants.
• Analysis of plasma membrane organization and phospholipid asymmetry in mutant strains.
• Assessment of cell permeability and susceptibility to membrane-damaging agents.
• Gene deletion studies to confirm the role of specific phospholipids in copper sensitivity.

Main Results:

• Overexpression of SUR7 rescued copper sensitivity in a mutant lacking MCC/eisosomes, highlighting the importance of these domains.
• New mutants with defects in membrane trafficking, actin cytoskeleton, and morphogenesis exhibited increased copper sensitivity.
• Copper-sensitive mutants showed increased plasma membrane permeabilization due to externalization of phosphatidylserine and phosphatidylethanolamine.
• Deletion of CHO1, which prevents phosphatidylserine synthesis, rescued the copper sensitivity of sur7Δ cells.

Conclusions:

• Proper plasma membrane architecture and phospholipid asymmetry are critical for protecting fungal pathogens from copper toxicity.
• Externalization of phosphatidylserine is a major contributor to copper sensitivity in Candida albicans.
• Targeting plasma membrane integrity presents a potential therapeutic strategy against fungal infections.