Mitochondrial Complex V α Subunit Is Critical for Candida albicans Pathogenicity through Modulating Multiple...

Area of Science:

• Molecular biology
• Mycology
• Infectious diseases

Background:

• Mitochondrial complex V's alpha subunit (ATP1) is essential for cellular ATP production.
• The role of ATP1 in Candida albicans pathogenicity is not well understood.
• Candida albicans is an opportunistic fungal pathogen causing various infections.

Purpose of the Study:

• To investigate the role of the ATP1 alpha subunit in Candida albicans pathogenicity.
• To compare the virulence of an ATP1 deletion mutant (atp1Δ/Δ) with wild-type (WT) and reconstituted strains.

Main Methods:

• Construction of ATP1 mutant (atp1Δ/Δ) and gene-reconstituted (atp1Δ/ATP1) Candida albicans strains.
• Assessment of pathogenicity in a murine model of disseminated candidiasis.
• In vitro assays evaluating fungal damage to host cells (macrophages, endothelial cells), growth under stress conditions (glucose deprivation, high H2O2), filamentation, and biofilm formation.

Main Results:

• Mice infected with atp1Δ/Δ showed significantly higher survival rates and lower fungal burden.
• The atp1Δ/Δ mutant exhibited reduced ability to damage host cells and impaired growth under stress conditions mimicking macrophage defense.
• Defects in filamentation and biofilm formation were observed in atp1Δ/Δ, alongside a significant drop in intracellular ATP levels.

Conclusions:

• The alpha subunit of mitochondrial complex V (ATP1) plays a significant role in Candida albicans pathogenicity.
• Loss of ATP1 compromises fungal virulence by affecting host cell interaction, stress resistance, and morphological transitions.
• ATP1 is a potential target for developing antifungal strategies against Candida albicans infections.