The conserved protein DopA is required for growth, drug tolerance and virulence in Aspergillus fumigatus.

Abstract

The majority of Aspergillus fumigatus reproduction occurs asexually, with large numbers of conidiophores producing small hydrophobic conidia dispersed aerially. When healthy hosts inhale conidia, the mucosal cilia and phagocytosis by the innate immune system can remove them. However, in immunocompromised hosts, the conidia are not removed, which allows them to germinate, forming mycelium that invades host tissues and causes disease. Previously we isolated a white A. fumigatus A1j strain incapable of producing conidia and screened several genes (including dopA) with significant expression differences and mutant loci in A1j. DopA homologous proteins in other species have been partially studied and are known to participate in various membrane transport-related cellular functions. Defects in these proteins in Saccharomyces cerevisiae, Caenorhabditis elegans, and Aspergillus nidulans result in defective cell morphology and abnormal growth. In this study, we observed reduced conidia production and abnormal development of spore-producing structures in the A. fumigatus dopA null strain, compared to parental strain, and demonstrated that dopA also modulates stress response and virulence of A. fumigatus.