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Infection and Immunity, September 2005, p. 5767-5774, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5767-5774.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Calcineurin Is Required for Candida albicans To Survive Calcium Stress in Serum

Departments of Molecular Genetics and Microbiology,¹ Medicine,² Pharmacology and Cancer Biology,³ Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710⁴

Received 31 January 2005/ Returned for modification 7 March 2005/ Accepted 27 April 2005

The calcium-activated protein phosphatase calcineurin plays a critical role in the virulence of Candida albicans. Previous studies demonstrated that calcineurin is not required for the yeast-hypha dimorphic transition, host cell adherence, or host cell injury, which are all established virulence attributes of this organism. Calcineurin is, however, essential for survival in serum and disseminated infection. Here we identify the component of serum that is toxic to calcineurin mutant cells. Proteins, peptides, lipids, and other hydrophobic components were all excluded as essential toxic elements. Upon testing of small molecules present in serum, we discovered that calcineurin protects cells from stress caused by the endogenous levels of calcium ions present in serum. These studies illustrate how calcineurin functions in a calcium homeostatic pathway that enables a common human commensal to survive passage through the hostile environment of the bloodstream to establish deep-seated infections and cause disease.

Editor: T. R. Kozel

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