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 cerevisiae, 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 resistance to cycloheximide, chloramphenicol and other drugs, such as the antifungal miconazole, with collateral hypersensitivity to oligomycin, nystatin and 2,4 dinitrophenol. Our results also demonstrate the presence of several PDR5 complementing genes in C. albicans, displaying multidrug-resistance patterns different from PDR5 and CDR1. The nucleotide 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 structural organization is characterized by two homologous halves, each comprising a hydrophobic region with a set of six transmembrane stretches, preceded by a hydrophilic nucleotide binding fold.
Prasad
R
R
Unite de Biochimie Physiologique, Universite Catholique de Louvain, Louvain-la-Neuve, Belgium.
De Wergifosse
P
P
Goffeau
A
A
Balzi
E
E
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000494:pharmacology; D001483:Base Sequence; D002176:Candida albicans / Q000235:genetics*; D003001:Cloning, Molecular; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology; D026901:Membrane Transport Proteins; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014170:Transformation, Genetic
D000935:Antifungal Agents; C094693:CDR1 protein, Candida albicans; D005656:Fungal Proteins; D026901:Membrane Transport Proteins