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Antimicrobial Agents and Chemotherapy, July 1998, p. 1695-1701, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Fluconazole Resistance Associated with Drug Efflux and Increased Transcription of a Drug Transporter Gene, PDH1, in Candida glabrata

Haruko Miyazaki,1 Yoshitsugu Miyazaki,1 Antonia Geber,1,2 Tanya Parkinson,3 Christopher Hitchcock,3 Derek J. Falconer,3 Douglas J. Ward,4 Katherine Marsden,1 and John E. Bennett1,*

Clinical Mycology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda,1 and Center for Biological Evaluation and Research, Food and Drug Administration, Rockville,2 Maryland; Department of Discovery Biology, Pfizer Central Research, Sandwich, United Kingdom3; and Dupont Circle Physicians Group, Washington, D.C.4

Received 1 October 1997/Returned for modification 31 March 1998/Accepted 8 May 1998

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.

* Corresponding author. Mailing address: Clinical Center, rm. 11C304, NIH, Bethesda, MD. 20892. Phone: (301) 496-3461. Fax: (301) 480-0050. E-mail: jb46y{at}nih.gov.

Antimicrobial Agents and Chemotherapy, July 1998, p. 1695-1701, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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