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Infect Immun, June 1998, p. 2713-2721, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Roles of the Candida albicans Mitogen-Activated Protein Kinase Homolog, Cek1p, in Hyphal Development and Systemic Candidiasisdagger

Csilla Csank,1,2,Dagger Klaus Schröppel,3 Ekkehard Leberer,1,4 Doreen Harcus,1 Othman Mohamed,1,5 Sylvain Meloche,2 David Y. Thomas,1,5 and Malcolm Whiteway1,5,*

Eukaryotic Genetics Group, National Research Council of Canada, Biotechnology Research Institute, Montreal, Quebec H4P 2R2,1 Centre de Recherche Hôtel-Dieu de l'Université de Montréal (CHUM) and Department of Pharmacology, University of Montreal, Montreal, Quebec H2W 1T8,2 and Department of Medicine4 and Department of Biology,5 McGill University, Montreal, Quebec H3A 1B1, Canada, and Institute of Clinical Microbiology and Immunology, University of Erlangen, D-91054 Erlangen, Germany3

Received 10 December 1997/Returned for modification 29 January 1998/Accepted 18 March 1998

Extracellular signal-regulated protein kinase (ERK, or mitogen-activated protein kinase [MAPK]) regulatory cascades in fungi turn on transcription factors that control developmental processes, stress responses, and cell wall integrity. CEK1 encodes a Candida albicans MAPK homolog (Cek1p), isolated by its ability to interfere with the Saccharomyces cerevisiae MAPK mating pathway. C. albicans cells with a deletion of the CEK1 gene are defective in shifting from a unicellular budding colonial growth mode to an agar-invasive hyphal growth mode when nutrients become limiting on solid medium with mannitol as a carbon source or on glucose when nitrogen is severely limited. The same phenotype is seen in C. albicans mutants in which the homologs (CST20, HST7, and CPH1) of the S. cerevisiae STE20, STE7, and STE12 genes are disrupted. In S. cerevisiae, the products of these genes function as part of a MAPK cascade required for mating and invasiveness of haploid cells and for pseudohyphal development of diploid cells. Epistasis studies revealed that the C. albicans CST20, HST7, CEK1, and CPH1 gene products lie in an equivalent, canonical, MAPK cascade. While Cek1p acts as part of the MAPK cascade involved in starvation-specific hyphal development, it may also play independent roles in C. albicans. In contrast to disruptions of the HST7 and CPH1 genes, disruption of the CEK1 gene adversely affects the growth of serum-induced mycelial colonies and attenuates virulence in a mouse model for systemic candidiasis.

* Corresponding author. Mailing address: Eukaryotic Genetics Group, National Research Council of Canada, Biotechnology Research Institute, 6100 Royalmount Ave., Montreal, Quebec H4P 2R2, Canada. Phone: (514) 496-6146. Fax: (514) 496-6213. E-mail: malcolm.whiteway{at}nrc.ca.

dagger National Research Council publication no. 41418.

Dagger Present address: Mitotix, Inc., Cambridge, MA 02139.

Infect Immun, June 1998, p. 2713-2721, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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