The high copper tolerance of Candida albicans is mediated by a P-type ATPase

The pathogenic: yeast Candida albicans has higher resistance than the baker 's yeast Saccharomyces cerevisiae to elevated concentrations of copper. To understand the basis of this differential resistance, we performed a functi onal screen for C albicans genes involved in copper detoxification. Here, w e report the isolation of two such genes: a metallothionein, CaCUP1, and a copper-transporting P-type ATPase, CaCRP1. Both genes are induced by extrac ellular copper. Gene disruptions indicated that the copper extrusion pump i s responsible for the unusual resistance of C, albicans to copper, whereas the metallothionein is responsible for the residual copper resistance of th e Cacrp1 Delta mutant. We show further that under acidic and anaerobic cond itions, such as prevail in the natural niche of C. albicans, the digestive tract of animals, CaCRP1 function becomes essential for survival in the pre sence of even very low copper concentrations. These observations suggest th at copper in the gastrointestinal tract may present a toxic challenge to wh ich enteric organisms had to adapt.