Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata.
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.
Miyazaki
H
H
Clinical Mycology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Miyazaki
Y
Y
Geber
A
A
Parkinson
T
T
Hitchcock
C
C
Falconer
D J
DJ
Ward
D J
DJ
Marsden
K
K
Bennett
J E
JE
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000382:microbiology; D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000494:pharmacology*; D001692:Biological Transport; D015152:Blotting, Northern; D015139:Blotting, Southern; D002175:Candida / Q000187:drug effects / Q000235:genetics*; D002177:Candidiasis / Q000150:complications / Q000382:microbiology; D004352:Drug Resistance, Microbial / Q000235:genetics; D015725:Fluconazole / Q000494:pharmacology*; D005656:Fungal Proteins; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D008969:Molecular Sequence Data; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid
D000935:Antifungal Agents; D005656:Fungal Proteins; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D015725:Fluconazole