Proper Sterol Distribution Is Required for <i>Candida albicans</i> Hyphal Formation and Virulence

Abstract

<i>Candida albicans</i> is an opportunistic fungus responsible for the majority of systemic fungal infections. Multiple factors contribute to <i>C. albicans</i> pathogenicity. <i>C. albicans</i> strains lacking CaArv1 are avirulent. Arv1 has a conserved Arv1 homology domain (AHD) that has a zinc-binding domain containing two cysteine clusters. Here, we explored the role of the CaAHD and zinc-binding motif in CaArv1-dependent virulence. Overall, we found that the CaAHD was necessary but not sufficient for cells to be virulent, whereas the zinc-binding domain was essential, as <i>Caarv1/Caarv1</i> cells expressing the full-length zinc-binding domain mutants, Caarv1^C3S and Caarv1^C28S, were avirulent. Phenotypically, we found a direct correlation between the avirulence of <i>Caarv1/Caarv1</i>, <i>Caarrv1^AHD</i> , <i>Caarv1^C3S</i> , and <i>Caarv1^C28S</i> cells and defects in bud site selection, septa formation and localization, and hyphal formation and elongation. Importantly, all avirulent mutant strains lacked the ability to maintain proper sterol distribution. Overall, our results have established the importance of the AHD and zinc-binding domain in fungal invasion, and have correlated an avirulent phenotype with the inability to maintain proper sterol distribution.