title: Arv1 lipid transporter function is conserved between pathogenic and nonpathogenic fungi.
abstract: The lipid transporter Arv1 regulates sterol trafficking, and glycosylphosphatidylinositol and sphingolipid biosyntheses in Saccharomyces cerevisiae. ScArv1 contains an Arv1 homology domain (AHD) that is conserved at the amino acid level in the pathogenic fungal species, Candida albicans and Candida glabrata. Here we show S. cerevisiae cells lacking Arv1 are highly susceptible to antifungal drugs. In the presence of drug, Scarv1 cells are unable to induce ERG gene expression, have an altered pleiotrophic drug response, and are defective in multi-drug resistance efflux pump expression. All phenotypes are remediated by ectopic expression of CaARV1 or CgARV1. The AHDs of these pathogenic fungi are required for specific drug tolerance, demonstrating conservation of function. In order to understand how Arv1 regulates antifungal susceptibility, we examined sterol trafficking. CaARV1/CgARV1 expression suppressed the sterol trafficking defect of Scarv1 cells. Finally, we show that C. albicansarv1/arv1 cells are avirulent using a BALB/c disseminated mouse model. We suggest that overall cell survival in response to antifungal treatment requires the lipid transporter function of Arv1.
authors.affiliation: Venenum Biodesign, Genesis Biotechnology Group, Hamilton, NJ 08691, United States.
authors.forename: Christina
authors.initials: C
authors.lastname: Gallo-Ebert
authors.forename: Paula C
authors.initials: PC
authors.lastname: McCourt
authors.forename: Melissa
authors.initials: M
authors.lastname: Donigan
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Villasmil
authors.forename: WeiWei
authors.initials: W
authors.lastname: Chen
authors.forename: Devanshi
authors.initials: D
authors.lastname: Pandya
authors.forename: Judith
authors.initials: J
authors.lastname: Franco
authors.forename: Desiree
authors.initials: D
authors.lastname: Romano
authors.forename: Sean G
authors.initials: SG
authors.lastname: Chadwick
authors.forename: Scott E
authors.initials: SE
authors.lastname: Gygax
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Nickels
mesh_terms: D000818:Animals; D000935:Antifungal Agents; D002176:Candida albicans / Q000235:genetics* / Q000472:pathogenicity*; D018432:Drug Resistance, Multiple / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D050356:Lipid Metabolism / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013261:Sterols / Q000378:metabolism*
chemical_list: C467736:ARV1 protein, S cerevisiae; D000935:Antifungal Agents; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols