Signal transduction through homologs of the Ste20p and Ste7p protein kinases can trigger hyphal formation in the pathogenic fungus Candida albicans.
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.
Leberer
E
E
Biotechnology Research Institute, National Research Council of Canada, Montreal, Canada. EKKEHARD.LEBERER@NRC.CA
Harcus
D
D
Broadbent
I D
ID
Clark
K L
KL
Dignard
D
D
Ziegelbauer
K
K
Schmidt
A
A
Gow
N A
NA
Brown
A J
AJ
Thomas
D Y
DY
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002176:Candida albicans / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D002177:Candidiasis / Q000503:physiopathology*; D016384:Consensus Sequence; D017931:DNA Primers; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D015698:Genomic Library; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020929:Mitogen-Activated Protein Kinase Kinases; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014774:Virulence
D017931:DNA Primers; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C119859:CST20 protein, Candida albicans; D017346:Protein Serine-Threonine Kinases; D020930:MAP Kinase Kinase Kinases; C078754:STE20 protein, S cerevisiae; C119846:HST7 protein, Candida albicans; D020929:Mitogen-Activated Protein Kinase Kinases; C119844:STE7 protein, S cerevisiae