IDENTIFICATION OF POLYMORPHIC MUTANT ALLELES OF CAMDR1, A MAJOR FACILITATOR OF CANDIDA-ALBICANS WHICH CONFERS MULTIDRUG-RESISTANCE, AND ITSIN-VITRO TRANSCRIPTIONAL ACTIVATION

CaMDR1 (Candida albicans Multi Drug Resistance) encodes a major facili tator whose expression in Saccharomyces cerevisiae confers resistance to several unrelated drugs. We describe here the identification and mo lecular characterization of seven mutant alleles of CaMDR1 (CaMDR1-1 t o 1-7). The complete sequencing of CaMDR1 alleles revealed several in- frame point mutations leading to a change in amino-acid residues where insertion/replacement of an aspartate residue in a serine-asparagine- aspartate-rich domain was most noteworthy. Interestingly, these allele s showed a distinct drug resistance profile. The expression of CaMDR1, or of its alleles, in C. albicans cells was enhanced by benomyl, meth otrexate and several other unrelated drugs, and was more pronounced in at least one of the azole-resistant clinical isolates.