Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata

Haruko Miyazaki, Yoshitsugu Miyazaki, Antonia Geber, Tanya Parkinson, Christopher Hitchcock, Derek J. Falconer, Douglas J. Ward, Katherine Marsden, John E. Bennett

Research output: Contribution to journalArticle

Abstract

Sequential Candida glabrata isolates were obtained from the mouth of a patient infected with human immunodeficiency virus type 1 who was receiving high doses of fluconazole for oropharyngeal thrush. Fluconazole-susceptible colonies were replaced by resistant colonies that exhibited both increased fluconazole efflux and increased transcripts of a gene which codes for a protein with 72.5% identity to Pdr5p, an ABC multidrug transporter in Saccharomyces cerevisiae. The deduced protein had a molecular mass of 175 kDa and was composed of two homologous halves, each with six putative transmembrane domains and highly conserved sequences of ATP-binding domains. When the earliest and most azole-susceptible isolate of C. glabrata from this patient was exposed to fluconazole, increased transcripts of the PDR5 homolog appeared, linking azole exposure to regulation of this gene.

Original languageEnglish (US)
Pages (from-to)1695-1701
Number of pages7
JournalAntimicrobial agents and chemotherapy
Volume42
Issue number7
StatePublished - Jul 1998

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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    Miyazaki, H., Miyazaki, Y., Geber, A., Parkinson, T., Hitchcock, C., Falconer, D. J., Ward, D. J., Marsden, K., & Bennett, J. E. (1998). Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata. Antimicrobial agents and chemotherapy, 42(7), 1695-1701.