Identification and Characterization of a Candida albicans Mating Pheromone

Abstract

Candida albicans, the most prevalent fungal pathogen of humans, has recently been shown to undergo mating. Here we describe a mating pheromone produced by C. albicans α cells and show that the gene which encodes it (MFα) is required for α cells, but not a cells, to mate. We also identify the receptor for this mating pheromone as the product of the STE2 gene and show that this gene is required for the mating of a cells, but not α cells. Cells of the a mating type respond to the α mating pheromone by producing long polarized projections, similar to those observed in bona fide mating mixtures of C. albicans a and α cells. During this process, transcription of approximately 62 genes is induced. Although some of these genes correspond to those induced in Saccharomyces cerevisiae by S. cerevisiae α-factor, most are specific to the C. albicans pheromone response. The most surprising class encode cell surface and secreted proteins previously implicated in virulence of C. albicans in a mouse model of disseminated candidiasis. This observation suggests that aspects of cell-cell communication in mating may have been evolutionarily adopted for host-pathogen interactions in C. albicans.

ACKNOWLEDGMENTS

Richard J. Bennett and M. Andrew Uhl contributed equally to this work.

We are grateful to Diane Inglis (UCSF), Joe DeRisi (UCSF), Mike Lorentz (MIT) and Gerald Fink (MIT) for the collaboration that produced the DNA microarrays used in this paper. We are also grateful to the Stanford Genome Technology Center (http://www-sequence.stanford.edu/group/candida ) for providing sequence data for C. albicans. We thank David Kadosh for communicating results prior to publication, Hiten Madhani and Diane Inglis for comments on the manuscript, and Annie Tsong, Anita Sil, Burk Braun, and Bethann Hromatika for help with the microarrays.

This work was supported in part by grants from the Burroughs Wellcome Fund (993218) and NIH (R01 AI49187) to A.D.J. Sequencing of the C. albicans genome was accomplished with the support of the NIDR and the Burroughs Wellcome Fund. M.G.M. is a Howard Hughes Medical Institute Fellow.