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 rec eiving high doses of fluconazole for oropharyngeal thrush. Fluconazole -susceptible colonies were replaced by resistant colonies that exhibit ed both increased fluconazole efflux and increased transcripts of a ge ne which codes for a protein with 72.5% identity to Pdr5p, an ABC mult idrug transporter in Saccharomyces cerevisiae. The deduced protein had a molecular mass of 175 kDa and was composed of two homologous halves , each,vith six putative transmembrane domains and highly conserved se quences of ATP-binding domains. When the earliest and most azole-susce ptible isolate of C. glabrata from this patient was exposed to flucona zole, increased transcripts of the PDR5 homolog appeared, linking azol e exposure to regulation of this gene.