ADH1 promotes Candida albicans pathogenicity by stimulating oxidative phosphorylation

Area of Science:

• Mycology
• Molecular Biology
• Pathogenesis

Background:

• Alcohol dehydrogenase I (ADH1) in Candida albicans catalyzes acetaldehyde to ethanol conversion.
• The role of Adh1p in fungal pathogenicity is not well understood despite its prevalence.

Purpose of the Study:

• To investigate the pathogenic roles of ADH1 in Candida albicans.
• To elucidate the underlying mechanisms of ADH1's role in fungal pathogenicity.

Main Methods:

• Constructed ADH1 deletion mutant using SAT1 flipper strategy.
• Assessed growth, viability, and pathogenicity in mouse, C. elegans, and G. mellonella models.
• Evaluated in vitro virulence factors (adhesion, hyphal formation, biofilm, CSH) and bioenergetics (ROS, mitochondrial potential, ATP).

Main Results:

• ADH1 deletion did not affect growth but enhanced host survival and reduced fungal burden.
• Deletion increased cell surface hydrophobicity (CSH) and decreased virulence factors and related gene expression.
• Lack of ADH1 increased ROS and decreased mitochondrial membrane potential and ATP, despite elevated oxygen consumption.

Conclusions:

• ADH1 is essential for Candida albicans pathogenicity.
• ADH1's role in pathogenicity involves its impact on mitochondrial oxidative phosphorylation.