Abstract
The RTA3 gene, coding for a member of the Rta1p-like lipid-translocating exporter family, is coordinately upregulated with the ATP-binding cassette transporter genes CDR1 and CDR2 in azole-resistant clinical isolates of Candida albicans that carry activating mutations in the transcription factor Tac1p. We show here that deleting RTA3 in an azole-resistant clinical isolate carrying a Tac1p-activating mutation lowered fluconazole resistance by 2-fold, while overexpressing RTA3 in an azole-susceptible clinical isolate resulted in enhanced fluconazole tolerance associated with trailing growth in a liquid microtiter plate assay. We also demonstrate that an Rta3p-green fluorescent protein (GFP) fusion protein localizes predominantly to the plasma membrane, consistent with a putative function for Rta3p as a lipid translocase.
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
MeSH terms
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Antifungal Agents / pharmacology*
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Candida albicans / drug effects*
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Candida albicans / genetics
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Candida albicans / growth & development
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Candida albicans / metabolism
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Drug Resistance, Fungal / genetics*
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Fluconazole / pharmacology*
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Fungal Proteins / genetics*
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Fungal Proteins / metabolism
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Gene Expression Regulation, Fungal*
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / metabolism
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Mutation
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Phospholipid Transfer Proteins / genetics*
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Phospholipid Transfer Proteins / metabolism
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transformation, Bacterial
Substances
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Antifungal Agents
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CDR1 protein, Candida albicans
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Fungal Proteins
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Membrane Transport Proteins
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Phospholipid Transfer Proteins
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Protein Isoforms
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Recombinant Fusion Proteins
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Transcription Factors
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Green Fluorescent Proteins
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Fluconazole