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

The filamentous fungus Aspergillus fumigatus is the most important pathogenic fungus among Aspergillus species associated with aspergillosis. A. fumigatus is exposed to diverse environmental stresses in the hosts during infection such as an excess of essential metal copper. To gain further insights into copper homeostasis, we generated an A. fumigatus laboratory evolved strain with increased fitness in copper stress, and identified the mutation in a Zn₂-Cys₆ type transcription factor clcA. We examined the role of clcA using the evolved and ∆clcA strains. The ∆clcA strain exhibited defective growth on minimal medium, PDA and copper-repleted medium, and defective conidiogenesis and conidial pigmentation. We found that clcA was required for the expressions of genes involved in conidiogenesis, conidial pigmentation, and transporters cdr1B and mfsB related to azole resistance. clcA was dispensable for the virulence in silkworm infection model. We report here that clcA plays an important role in hyphal growth, conidiogenesis, and copper adaptation.