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

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

^*Department of Molecular Microbiology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel; and ^†National Institute of Oceanography, Haifa 31080, Israel

Edited by JoAnne Stubbe, Massachusetts Institute of Technology, Cambridge, MA, and approved January 14, 2000 (received for review October 19, 1999)

Abstract

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 functional screen for C. albicans genes involved in copper detoxification. Here, we report the isolation of two such genes: a metallothionein, CaCUP1, and a copper-transporting P-type ATPase, CaCRP1. Both genes are induced by extracellular copper. Gene disruptions indicated that the copper extrusion pump is responsible for the unusual resistance of C. albicans to copper, whereas the metallothionein is responsible for the residual copper resistance of the Cacrp1Δ mutant. We show further that under acidic and anaerobic conditions, such as prevail in the natural niche of C. albicans, the digestive tract of animals, CaCRP1 function becomes essential for survival in the presence of even very low copper concentrations. These observations suggest that copper in the gastrointestinal tract may present a toxic challenge to which enteric organisms had to adapt.

Footnotes

↵ ‡ To whom reprint requests should be addressed. E-mail: danielk{at}tx.technion.ac.il.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF193508 and AF193509).
Abbreviations:

MIC,

minimal inhibitory concentration;

GFP,

green fluorescent protein