A novel Zn₂-Cys₆ transcription factor clcA contributes to copper homeostasis in Aspergillus fumigatus

Area of Science:

• Medical Mycology
• Molecular Biology
• Environmental Microbiology

Background:

• Aspergillus fumigatus is a significant human pathogen causing aspergillosis.
• Fungal pathogens face environmental stresses, including excess copper, during host infection.
• Copper homeostasis is vital for fungal survival and pathogenicity.

Purpose of the Study:

• To investigate the role of the Zn2-Cys6 transcription factor clcA in copper homeostasis and stress adaptation in A. fumigatus.
• To identify genetic adaptations conferring increased fitness under copper stress.

Main Methods:

• Laboratory evolution of A. fumigatus under copper stress.
• Genetic analysis of evolved strains to identify mutations, focusing on the clcA gene.
• Phenotypic characterization of wild-type, evolved, and clcA deletion (∆clcA) strains.
• Gene expression analysis to determine clcA-regulated genes.

Main Results:

• A mutation in the clcA gene was identified in a laboratory-evolved strain with enhanced copper stress tolerance.
• The ∆clcA strain showed impaired hyphal growth, conidiogenesis, and conidial pigmentation.
• clcA regulates genes involved in conidiogenesis, pigmentation, and azole resistance transporters (cdr1B, mfsB).
• clcA is essential for copper adaptation but not for virulence in a silkworm infection model.

Conclusions:

• The transcription factor clcA plays a critical role in Aspergillus fumigatus hyphal growth, conidiogenesis, and adaptation to copper stress.
• Understanding clcA function provides targets for controlling A. fumigatus infections by modulating copper homeostasis.
• clcA is a key regulator of fungal development and stress response pathways.