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
-
Morphogenesis in Candida albicans.
Crit Rev Microbiol. 1985;12(1):45-93
PMID: 3893894
-
Antimycotic activity of BAY N 7133 in animal experiments.
J Antimicrob Chemother. 1984 May;13(5):447-63
PMID: 6330018
-
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
-
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
-
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
-
Isogenic strain construction and gene mapping in Candida albicans.
Genetics. 1993 Jul;134(3):717-28
PMID: 8349105
-
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
-
Elements of the yeast pheromone response pathway required for filamentous growth of diploids.
Science. 1993 Dec 10;262(5140):1741-4
PMID: 8259520
-
A brain serine/threonine protein kinase activated by Cdc42 and Rac1.
Nature. 1994 Jan 6;367(6458):40-6
PMID: 8107774
-
The role of cell-mediated immunity in candidiasis.
Trends Microbiol. 1994 Jun;2(6):202-6
PMID: 8087452
-
Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog.
Science. 1994 Dec 9;266(5191):1723-6
PMID: 7992058
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
Structure and regulation of the Candida albicans ADH1 gene encoding an immunogenic alcohol dehydrogenase.
Yeast. 1996 Feb;12(2):115-27
PMID: 8686375
-
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
-
DNA sequencing with chain-terminating inhibitors.
Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7
PMID: 271968
-
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