Arv1 lipid transporter function is conserved between pathogenic and nonpathogenic fungi
Christina Gallo-Ebert, Paula C. McCourt, Melissa Donigan, Michelle L. Villasmil, WeiWei Chen, Devanshi Pandya, Judith Franco, Desiree Romano, Sean G. Chadwick, Scott E. Gygax, …
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. albicans arv1/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. (C) 2011 Elsevier Inc. All rights reserved.
Arv1 lipid transporter function is conserved between pathogenic and nonpathogenic fungi
Creators
Christina Gallo-Ebert - Ansys
Paula C. McCourt - Ansys
Melissa Donigan - Ansys
Michelle L. Villasmil - Ansys
WeiWei Chen - Ansys
Devanshi Pandya - Ansys
Judith Franco - Ansys
Desiree Romano - Ansys
Sean G. Chadwick - Medical Diagnostic Laboratories (United States)
Scott E. Gygax - Medical Diagnostic Laboratories (United States)
Joseph T. Nickels - Ansys
Publication Details
Fungal genetics and biology, v 49(2), pp 101-113
Publisher
Elsevier
Number of pages
13
Grant note
HL67401 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
R01HL067401 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
Genesis Biotechnology Group
Resource Type
Journal article
Language
English
Academic Unit
Biochemistry and Molecular Biology
Web of Science ID
WOS:000300749000002
Scopus ID
2-s2.0-84863081183
Other Identifier
991021229987104721
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