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 Candida albicans was addressed through the characterization of C. albicans strains 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 susceptibility to some compounds such as nikkomycin Z or Congo red, which interfere with 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, consistently with this behavior, that HOG1 overexpression in Saccharomyces cerevisiae represses the pseudodimorphic transition. Most interestingly, deletion of HOG1 resulted in a drastic increase in the mean survival time of systemically infected mice, supporting a role for this MAP kinase pathway in virulence of pathogenic fungi. This finding has potential implications in antifungal therapy.
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D001798:Blood Proteins / Q000494:pharmacology; D001921:Brain / Q000382:microbiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002176:Candida albicans / Q000201:enzymology / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity*; D002177:Candidiasis / Q000382:microbiology*; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D002688:Chitinases / Q000378:metabolism; D003224:Congo Red / Q000494:pharmacology; D017353:Gene Deletion; D005800:Genes, Fungal; D020022:Genetic Predisposition to Disease; D007668:Kidney / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008854:Microscopy, Electron; D020928:Mitogen-Activated Protein Kinases; D009024:Morphogenesis; D009994:Osmolar Concentration; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins