Arv1 lipid transporter function is conserved between pathogenic and nonpathogenic fungi
| Autor: | Desiree R Romano, Melissa Donigan, Weiwei Chen, Christina Gallo-Ebert, Sean G. Chadwick, Michelle L. Villasmil, Joseph T. Nickels, Devanshi Pandya, Paula McCourt, Scott E. Gygax, Judith Franco |
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| Rok vydání: | 2012 |
| Předmět: |
Antifungal Agents
Saccharomyces cerevisiae Proteins Saccharomyces cerevisiae Microbiology Article Mice Gene Expression Regulation Fungal Candida albicans Gene expression Genetics Animals Sequence Homology Amino Acid biology Candida glabrata Membrane Proteins Lipid Metabolism biology.organism_classification Sphingolipid Drug Resistance Multiple Sterol Protein Transport Sterols Ectopic expression Efflux |
| Zdroj: | Fungal Genetics and Biology. 49:101-113 |
| ISSN: | 1087-1845 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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