The RTA3 gene, encoding a putative lipid translocase, influences the susceptibility of Candida albicans to fluconazole

Sarah G. Whaley, Sarah Tsao, Sandra Weber, Qing Zhang, Katherine S. Barker, Martine Raymond, Phillip Rogers

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)6060-6066
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number10
DOIs
StatePublished - Oct 1 2016

Fingerprint

Azoles
Fluconazole
Candida albicans
Lipids
Genes
Mutation
ATP-Binding Cassette Transporters
Green Fluorescent Proteins
Transcription Factors
Cell Membrane
Growth
Proteins

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

The RTA3 gene, encoding a putative lipid translocase, influences the susceptibility of Candida albicans to fluconazole. / Whaley, Sarah G.; Tsao, Sarah; Weber, Sandra; Zhang, Qing; Barker, Katherine S.; Raymond, Martine; Rogers, Phillip.

In: Antimicrobial Agents and Chemotherapy, Vol. 60, No. 10, 01.10.2016, p. 6060-6066.

Research output: Contribution to journalArticle

Whaley, Sarah G. ; Tsao, Sarah ; Weber, Sandra ; Zhang, Qing ; Barker, Katherine S. ; Raymond, Martine ; Rogers, Phillip. / The RTA3 gene, encoding a putative lipid translocase, influences the susceptibility of Candida albicans to fluconazole. In: Antimicrobial Agents and Chemotherapy. 2016 ; Vol. 60, No. 10. pp. 6060-6066.
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