title: The RTA3 Gene, Encoding a Putative Lipid Translocase, Influences the Susceptibility of Candida albicans to Fluconazole.
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.
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Whaley
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Tsao
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Sandra
authors.initials: S
authors.lastname: Weber
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Barker
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec, Canada martine.raymond@umontreal.ca drogers@uthsc.edu.
authors.forename: Martine
authors.initials: M
authors.lastname: Raymond
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA martine.raymond@umontreal.ca drogers@uthsc.edu.
authors.forename: P David
authors.initials: PD
authors.lastname: Rogers
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D025141:Drug Resistance, Fungal / Q000235:genetics*; D015725:Fluconazole / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D049294:Phospholipid Transfer Proteins / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014169:Transformation, Bacterial
chemical_list: D000935:Antifungal Agents; C094693:CDR1 protein, Candida albicans; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D049294:Phospholipid Transfer Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D015725:Fluconazole