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PMID: 8917571 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Signal transduction through homologs of the Ste20p and Ste7p protein kinases can trigger hyphal formation in the pathogenic fungus Candida albicans.

Leberer E, Harcus D, Broadbent ID, Clark KL, Dignard D, Ziegelbauer K, Schmidt A, Gow NA, Brown AJ, Thomas DY

Abstract

The CST20 gene of Candida albicans was cloned by functional complementation of a deletion of the STE20 gene in Saccharomyces cerevisiae. CST20 encodes a homolog of the Ste20p/p65PAK family of protein kinases. Colonies of C. albicans cells deleted for CST20 revealed defects in the lateral formation of mycelia on synthetic solid "Spider" media. However, hyphal development was not impaired in some other media. A similar phenotype was caused by deletion of HST7, encoding a functional homolog of the S. cerevisiae Ste7p protein kinase. Overexpression of HST7 partially complemented the deletion of CST20. Cells deleted for CST20 were less virulent in a mouse model for systemic candidiasis. Our results suggest that more than one signaling pathway can trigger hyphal development in C. albicans, one of which has a protein kinase cascade that is analogous to the mating response pathway in S. cerevisiae and might have become adapted to the control of mycelial formation in asexual C. albicans.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Candida albicans/genetics,pathogenicity,physiology Candidiasis/physiopathology Consensus Sequence DNA Primers Fungal Proteins/genetics,metabolism Gene Deletion Genes, Fungal Genetic Complementation Test Genomic Library Intracellular Signaling Peptides and Proteins MAP Kinase Kinase Kinases Male Mice Mice, Inbred Strains Mitogen-Activated Protein Kinase Kinases Molecular Sequence Data Polymerase Chain Reaction Protein Kinases/biosynthesis,chemistry,genetics,metabolism,physiology Protein Serine-Threonine Kinases/biosynthesis,physiology Saccharomyces cerevisiae/genetics,growth & development Saccharomyces cerevisiae Proteins Sequence Homology, Amino Acid Signal Transduction Virulence
Chemicals
DNA Primers Fungal Proteins Intracellular Signaling Peptides and Proteins Saccharomyces cerevisiae Proteins Protein Kinases CST20 protein, Candida albicans Protein Serine-Threonine Kinases MAP Kinase Kinase Kinases STE20 protein, S cerevisiae HST7 protein, Candida albicans Mitogen-Activated Protein Kinase Kinases STE7 protein, S cerevisiae
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Leberer E
Biotechnology Research Institute, National Research Council of Canada, Montreal, Canada. [email protected]
Harcus D
Broadbent I D
Clark K L
Dignard D
Ziegelbauer K
Schmidt A
Gow N A
Brown A J
Thomas D Y
References (24)
24 references, click to expand
  1. Morphogenesis in Candida albicans.
    Crit Rev Microbiol. 1985;12(1):45-93 PMID: 3893894
  2. Antimycotic activity of BAY N 7133 in animal experiments.
    J Antimicrob Chemother. 1984 May;13(5):447-63 PMID: 6330018
  3. Isolation from Candida albicans of a functional homolog of the Saccharomyces cerevisiae KRE1 gene, which is involved in cell wall beta-glucan synthesis.
    J Bacteriol. 1991 Nov;173(21):6859-64 PMID: 1938890
  4. Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS.
    Cell. 1992 Mar 20;68(6):1077-90 PMID: 1547504
  5. The protein kinase homologue Ste20p is required to link the yeast pheromone response G-protein beta gamma subunits to downstream signalling components.
    EMBO J. 1992 Dec;11(13):4815-24 PMID: 1464311
  6. Isogenic strain construction and gene mapping in Candida albicans.
    Genetics. 1993 Jul;134(3):717-28 PMID: 8349105
  7. Cloning of Saccharomyces cerevisiae STE5 as a suppressor of a Ste20 protein kinase mutant: structural and functional similarity of Ste5 to Far1.
    Mol Gen Genet. 1993 Nov;241(3-4):241-54 PMID: 8246877
  8. Elements of the yeast pheromone response pathway required for filamentous growth of diploids.
    Science. 1993 Dec 10;262(5140):1741-4 PMID: 8259520
  9. A brain serine/threonine protein kinase activated by Cdc42 and Rac1.
    Nature. 1994 Jan 6;367(6458):40-6 PMID: 8107774
  10. The role of cell-mediated immunity in candidiasis.
    Trends Microbiol. 1994 Jun;2(6):202-6 PMID: 8087452
  11. Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog.
    Science. 1994 Dec 9;266(5191):1723-6 PMID: 7992058
  12. Elements of a single MAP kinase cascade in Saccharomyces cerevisiae mediate two developmental programs in the same cell type: mating and invasive growth.
    Genes Dev. 1994 Dec 15;8(24):2974-85 PMID: 8001818
  13. Avirulence of Candida albicans auxotrophic mutants in a rat model of oropharyngeal candidiasis.
    FEMS Microbiol Lett. 1995 Feb 15;126(2):177-80 PMID: 7705609
  14. The CUG codon is decoded in vivo as serine and not leucine in Candida albicans.
    Nucleic Acids Res. 1995 May 11;23(9):1481-6 PMID: 7784200
  15. Shk1, a homolog of the Saccharomyces cerevisiae Ste20 and mammalian p65PAK protein kinases, is a component of a Ras/Cdc42 signaling module in the fission yeast Schizosaccharomyces pombe.
    Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6180-4 PMID: 7597098
  16. Molecular characterization of Ste20p, a potential mitogen-activated protein or extracellular signal-regulated kinase kinase (MEK) kinase kinase from Saccharomyces cerevisiae.
    J Biol Chem. 1995 Jul 7;270(27):15984-92 PMID: 7608157
  17. Ste20-like protein kinases are required for normal localization of cell growth and for cytokinesis in budding yeast.
    Genes Dev. 1995 Aug 1;9(15):1817-30 PMID: 7649470
  18. Pheromone signalling in Saccharomyces cerevisiae requires the small GTP-binding protein Cdc42p and its activator CDC24.
    Mol Cell Biol. 1995 Oct;15(10):5246-57 PMID: 7565673
  19. Fission yeast pak1+ encodes a protein kinase that interacts with Cdc42p and is involved in the control of cell polarity and mating.
    EMBO J. 1995 Dec 1;14(23):5908-19 PMID: 8846783
  20. Constitutive activation of the Saccharomyces cerevisiae mating response pathway by a MAP kinase kinase from Candida albicans.
    Mol Gen Genet. 1995 Dec 20;249(6):609-21 PMID: 8544826
  21. Structure and regulation of the Candida albicans ADH1 gene encoding an immunogenic alcohol dehydrogenase.
    Yeast. 1996 Feb;12(2):115-27 PMID: 8686375
  22. An amino acid liquid synthetic medium for the development of mycelial and yeast forms of Candida Albicans.
    Sabouraudia. 1975 Jul;13(2):148-53 PMID: 808868
  23. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  24. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae.
    Genetics. 1989 May;122(1):19-27 PMID: 2659436
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1996-11-12
Pages
13217-22
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24073
Subset
IM
Databases
GENBANK
L47210
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