Prasad R, De Wergifosse P, Goffeau A, Balzi E
Unite de Biochimie Physiologique, Universite Catholique de Louvain, Louvain-la-Neuve, Belgium.
Curr Genet. 1995 Mar;27(4):320-9. doi: 10.1007/BF00352101.
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.
通过对酿酒酵母PDR5缺失突变体进行功能互补，我们克隆并测序了白色念珠菌的多药耐药基因CDR1。用CDR1转化对环己酰亚胺和氯霉素敏感的PDR5缺失宿主，使其对环己酰亚胺、氯霉素和其他药物（如抗真菌药咪康唑）产生抗性，同时对寡霉素、制霉菌素和2,4-二硝基苯酚产生附带敏感性。我们的结果还证明白色念珠菌中存在几个PDR5互补基因，它们显示出与PDR5和CDR1不同的多药耐药模式。CDR1的核苷酸序列显示，与PDR5一样，它编码一个属于ABC（ATP结合盒）超家族的假定膜泵。CDR1编码一个由1501个氨基酸组成、分子量为169.9 kDa的蛋白质，其预测的结构组织特征是由两个同源部分组成，每个部分包含一个带有一组六个跨膜区段的疏水区域，前面是一个亲水性核苷酸结合结构域。
