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 fl...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 1998-07, Vol.42 (7), p.1695-1701
Main Authors: MIYAZAKI, H, MIYAZAKI, Y, GEBER, A, PARKINSON, T, HITCHCOCK, C, FALCONER, D. J, WARD, D. J, MARSDEN, K, BENNETT, J. E
Format: Article
Language:English
Subjects:
AIDS-Related Opportunistic Infections - drug therapy
AIDS-Related Opportunistic Infections - microbiology
AIDS/HIV
Amino Acid Sequence
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antifungal agents
Antifungal Agents - pharmacology
Biological and medical sciences
Biological Transport
Blotting, Northern
Blotting, Southern
Candida - drug effects
Candida - genetics
Candidiasis - complications
Candidiasis - microbiology
Drug Resistance, Microbial - genetics
Fluconazole - pharmacology
Fungal Proteins
Humans
Male
Mechanisms of Action: Physiological Effects
Medical sciences
Membrane Proteins - genetics
Membrane Proteins - physiology
Middle Aged
Molecular Sequence Data
Pharmacology. Drug treatments
Saccharomyces cerevisiae Proteins
Sequence Homology, Amino Acid
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Summary: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.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.42.7.1695