The vesicle transport protein Vac1p is required for virulence of Candida albicans

Abstract

The putative vesicle transport protein Vac1p of the human pathogenic yeastCandida albicansplays an important role in virulence. To determine the cellular functions of Vac1p, a null mutant was generated by sequential disruption of both alleles. Thevac1null mutant strain showed defective endosomal vesicle transport, demonstrating a role of Vac1p in protein transport to the vacuole. Vac1p also contributes to resistance to metal ions, as the null mutant strain was hypersensitive to Cu2+, Zn2+and Ni2+. In addition, the loss of Vac1p affected several virulence factors ofC. albicans. In particular, thevac1null mutant strain showed defective hyphal growth, even when hyphal formation was induced via different pathways. Furthermore, Vac1p affects chlamydospore formation, adherence to human vaginal epithelial cells, and the secretion of aspartyl proteinases (Saps). Avirulence in a mouse model of systemic infection of thevac1null mutant strongly suggests that Vac1p ofC. albicansis essential for pathogenicity. In summary, the Vac1p protein is required for several cellular pathways, in particular those that control virulence and pathogenicity. Consequently, Vac1p is a novel and interesting target for antifungal drugs.