title: Protein phosphatase CaPpz1 is involved in cation homeostasis, cell wall integrity and virulence of Candida albicans.
abstract: The opportunistic pathogen Candida albicans has a single protein phosphatase Z (PPZ) candidate gene termed CaPPZ1, which shows significant allele variability. We demonstrate here that bacterially expressed CaPpz1 protein exhibits phosphatase activity which can be inhibited by recombinant Hal3, a known inhibitor of Saccharomyces cerevisiae Ppz1. Site-directed mutagenesis experiments based on natural polymorphisms allowed the identification of three amino acid residues that affect enzyme activity or stability. The expression of CaPPZ1 in ppz1 S. cerevisiae and pzh1 Schizosaccharomyces pombe cells partially rescued the salt and caffeine phenotypes of the deletion mutants. CaPpz1 also complemented the slt2 S. cerevisiae mutant, which is crippled in the mitogen-activated protein (MAP) kinase that mediates the cell wall integrity signalling pathway. Collectively, our results suggest that the orthologous PPZ enzymes have similar but not identical functions in different fungi. The deletion of the CaPPZ1 gene in C. albicans resulted in a mutant that was sensitive to salts such as LiCl and KCl, to caffeine, and to agents that affect cell wall biogenesis such as Calcofluor White and Congo red, but was tolerant to spermine and hygromycin B. Reintegration of the CaPPZ1 gene into the deletion mutant alleviated all of the mutant phenotypes tested. Thus CaPpz1 is involved in cation homeostasis, cell wall integrity and the regulation of the membrane potential of C. albicans. In addition, the germ tube growth rate, and virulence in the BALB/c mouse model, were reduced in the null mutant, suggesting a novel function for CaPpz1 in the yeast to hypha transition that may have medical relevance.
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, Research Centre for Molecular Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Ádám
authors.affiliation: Department of Microbial Biotechnology and Cell Biology, Faculty of Science, University of Debrecen, Debrecen, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Erdei
authors.affiliation: Institut de Biotecnología i Biomedicina, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma Barcelona, Cerdanyola del Vallès, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Casado
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, Research Centre for Molecular Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Kovács
authors.affiliation: Institut de Biotecnología i Biomedicina, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma Barcelona, Cerdanyola del Vallès, Spain.
authors.forename: Asier
authors.initials: A
authors.lastname: González
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Majoros
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, Research Centre for Molecular Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Petrényi
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Bagossi
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, Research Centre for Molecular Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Ilona
authors.initials: I
authors.lastname: Farkas
authors.affiliation: Department of Microbial Biotechnology and Cell Biology, Faculty of Science, University of Debrecen, Debrecen, Hungary.
authors.forename: Monika
authors.initials: M
authors.lastname: Molnar
authors.affiliation: Department of Microbial Biotechnology and Cell Biology, Faculty of Science, University of Debrecen, Debrecen, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Pócsi
authors.affiliation: Institut de Biotecnología i Biomedicina, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma Barcelona, Cerdanyola del Vallès, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Ariño
authors.affiliation: Cell Biology and Signalling Research Group of the Hungarian Academy of Sciences, University of Debrecen, Debrecen, Hungary.|Department of Medical Chemistry, Faculty of Medicine, Research Centre for Molecular Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Viktor
authors.initials: V
authors.lastname: Dombrádi
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D002473:Cell Wall / Q000378:metabolism*; D003001:Cloning, Molecular; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005816:Genetic Complementation Test; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D010749:Phosphoprotein Phosphatases