title: Proper Sterol Distribution Is Required forCandida albicansHyphal Formation and Virulence.
abstract: Candida albicansis an opportunistic fungus responsible for the majority of systemic fungal infections. Multiple factors contribute toC. albicanspathogenicity.C. albicansstrains 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, asCaarv1/Caarv1cells expressing the full-length zinc-binding domain mutants, Caarv1C3Sand Caarv1C28S, were avirulent. Phenotypically, we found a direct correlation between the avirulence ofCaarv1/Caarv1,Caarrv1AHD,Caarv1C3S, andCaarv1C28Scells 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.
authors: The Institute of Metabolic Disorders, Genesis Biotechnology Group, Hamilton, New Jersey 08691.
authors: Paula
authors: P
authors: McCourt
authors: The Institute of Metabolic Disorders, Genesis Biotechnology Group, Hamilton, New Jersey 08691.
authors: Hsing-Yin
authors: HY
authors: Liu
authors: Centre for Cytochrome P450 Biodiversity, Institute of Life Sciences and School of Medicine, Swansea University Medical School, SA2 8PP, UK.
authors: Josie E
authors: JE
authors: Parker
authors: The Institute of Metabolic Disorders, Genesis Biotechnology Group, Hamilton, New Jersey 08691.
authors: Christina
authors: C
authors: Gallo-Ebert
authors: The Institute of Metabolic Disorders, Genesis Biotechnology Group, Hamilton, New Jersey 08691.
authors: Melissa
authors: M
authors: Donigan
authors: Invivotek, Genesis Biotechnology Group, Hamilton, New Jersey 08691.
authors: Adam
authors: A
authors: Bata
authors: Invivotek, Genesis Biotechnology Group, Hamilton, New Jersey 08691.
authors: Caroline
authors: C
authors: Giordano
authors: Centre for Cytochrome P450 Biodiversity, Institute of Life Sciences and School of Medicine, Swansea University Medical School, SA2 8PP, UK.
authors: Steven L
authors: SL
authors: Kelly
authors: The Institute of Metabolic Disorders, Genesis Biotechnology Group, Hamilton, New Jersey 08691 jnickels@venenumbiodesign.com.
authors: Joseph T
authors: JT
authors: Nickels
keywords: Candida; hyphae; lipid; sterol; virulence