A putative dual-specific protein phosphatase encoded by YVH1 controls growth, filamentation and virulence in Candida...

In response to stimulants, such as serum, the yeast cells of the opportunistic fungal pathogen Candida albicans form germ tubes, which develop into hyphae. Yvh1p, one of the 29 protein phosphatases encoded in the C. albicans genome, has 45% identity with the dual-specific phosphatase Yvh1p of the model yeast Saccharomyces cerevisiae. In this study, Yvh1p expression was not observed during the initial step of germ tube formation, although Yvh1p was expressed constitutively in cell cycle progression of yeast or hyphal cells. In an attempt to analyse the function of Yvh1p phosphatase, the complete ORFs of both alleles were deleted by replacement with hph200-URA3-hph200 and ARG4. Although YVH1 has nine single-nucleotide polymorphisms in its coding sequence, both YVH1 alleles were able to complement the YVH1 gene disruptant. The vegetative growth of Deltayvh1 was significantly slower than the wild-type. The hyphal growth of Deltayvh1 on agar, or in a liquid medium, was also slower than the wild-type because of the delay in nuclear division and septum formation, although germ tube formation was similar between the wild-type and the disruptant. Despite the slow hyphal growth, the expression of several hypha-specific genes in Deltayvh1 was not delayed or repressed compared with that of the wild-type. Infection studies using mouse models revealed that the virulence of Deltayvh1 was less than that of the wild-type. Thus, YVH1 contributes to normal vegetative yeast or hyphal cell cycle progression and pathogenicity, but not to germ tube formation.