Derepressed hyphal growth and reduced virulence in a VH1 family-related protein phosphatase mutant of the human pathogen Candida albicans.
Mitogen-activated protein (MAP) kinases are pivotal components of eukaryotic signaling cascades. Phosphorylation of tyrosine and threonine residues activates MAP kinases, but either dual-specificity or monospecificity phosphatases can inactivate them. The Candida albicans CPP1 gene, a structural member of the VH1 family of dual- specificity phosphatases, was previously cloned by its ability to block the pheromone response MAP kinase cascade in Saccharomyces cerevisiae. Cpp1p inactivated mammalian MAP kinases in vitro and acted as a tyrosine-specific enzyme. In C. albicans a MAP kinase cascade can trigger the transition from the budding yeast form to a more invasive filamentous form. Disruption of the CPP1 gene in C. albicans derepressed the yeast to hyphal transition at ambient temperatures, on solid surfaces. A hyphal growth rate defect under physiological conditions in vitro was also observed and could explain a reduction in virulence associated with reduced fungal burden in the kidneys seen in a systemic mouse model. A hyper-hyphal pathway may thus have some detrimental effects on C. albicans cells. Disruption of the MAP kinase homologue CEK1 suppressed the morphological effects of the CPP1 disruption in C. albicans. The results presented here demonstrate the biological importance of a tyrosine phosphatase in cell-fate decisions and virulence in C. albicans.
Csank
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Centre de Recherche, Hôtel-Dieu de Montréal and Department of Pharmacology, University of Montreal, Montreal, Quebec, Canada H2W 1T8.
Makris
C
C
Meloche
S
S
Schröppel
K
K
Röllinghoff
M
M
Dignard
D
D
Thomas
D Y
DY
Whiteway
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D002177:Candidiasis / Q000382:microbiology; D002455:Cell Division; D048429:Cell Size; D054637:Dual-Specificity Phosphatases; D005260:Female; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D007668:Kidney / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D016415:Sequence Alignment; D013172:Spores, Fungal / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity; D013696:Temperature; D014774:Virulence / Q000235:genetics
D005656:Fungal Proteins; C077339:CEK1 protein, Candida albicans; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C489855:dual specificity phosphatase 12; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases