MOLECULAR-CLONING AND CHARACTERIZATION OF A NOVEL GENE OF CANDIDA-ALBICANS, CDR1, CONFERRING MULTIPLE RESISTANCE TO DRUGS AND ANTIFUNGALS

By functional complementation of a PDR5 null mutant of Saccharomyces c erev isiae, we have cloned and sequenced the multidrug-resistance gene CDR1 of Candida albicans. Transformation by CDR1 of a PDR5-disrupted host hypersensitive to cycloheximide and chloramphenicol resulted in r esistance to cycloheximide, chloramphenicol and other drugs, such as t he antifungal miconazole, with collateral hypersensitivity to oligomyc in, nystatin and 2,4 dinitrophenol. Our results also demonstrate the p resence of several PDR5 complementing genes in C. albicans, displaying multidrug-resistance patterns different from PDR5 and CDR1. The nucle otide sequence of CDR1 revealed that, like PDR5, it encodes a putative membrane pump belonging to the ABC (ATP-binding cassette) superfamily . CDR1 encodes a 1501-residue protein of 169.9 kDa whose predicted str uctural organization is characterized by two homologous halves, each c omprising a hydrophobic region with a set of six transmembrane stretch es, preceded by a hydrophilic nucleotide binding fold.