Role of the mitogen-activated protein kinase hog1p in morphogenesis and virulence of Candida albicans

The relevance of the mitogen-activated protein (MAP) kinase Hog1p in Candid a albicans was addressed through the characterization of C, albicans strain s without a functional HOG1 gene. Analysis of the phenotype of hog1 mutants under osmostressing conditions revealed that this mutant displays a set of morphological alterations as the result of a failure to complete the final stages of cytokinesis, with parallel defects in the budding pattern. Even under permissive conditions, hog1 mutants displayed a different susceptibil ity to some compounds such as nikkomycin Z or Congo red, which interfere wi th cell wall functionality. In addition, the hog1 mutant displayed a colony morphology different from that of the wild-type strain on some media which promote morphological transitions in C. albicans. We show that C. albicans hog1 mutants are derepressed in the serum-induced hyphal formation and, co nsistently with this behavior, that HOG1 overexpression in Saccharomyces ce revisiae represses the pseudodimorphic transition. Most interestingly, dele tion of HOG1 resulted in a drastic increase in the mean survival time of sy stemically infected mice, supporting a role for this MAP kinase pathway in virulence of pathogenic fungi. This finding has potential implications in a ntifungal therapy.