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 euka ryotic signaling cascades. Phosphorylation of tyrosine and threonine r esidues activates MAP kinases, but either dual-specificity or monospec ificity phosphatases can inactivate them. The Candida albicans CPP1 ge ne, a structural member of the VH1 family of dual-specificity phosphat ases, was previously cloned by its ability to block the pheromone resp onse MAP kinase cascade in Saccharomyces cerevisiae. Cpp1p inactivated mammalian MAP kinases in vitro and acted as a tyrosine-specific enzym e. In C. albicans a MAP kinase cascade can trigger the transition from the budding yeast form to a more invasive filamentous form. Disruptio n of the CPP1 gene in C. albicans derepressed the yeast to hyphal tran sition at ambient temperatures, on solid surfaces. A hyphal growth rat e 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. D isruption of the MAP kinase homologue CEK1 suppressed the morphologica l 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.