title: Candida glabrata Ste20 is involved in maintaining cell wall integrity and adaptation to hypertonic stress, and is required for wild-type levels of virulence.
abstract: The conserved family of fungal Ste20 p21-activated serine-threonine protein kinases regulate several signalling cascades. In Saccharomyces cerevisiae Ste20 is involved in pheromone signalling, invasive growth, the hypertonic stress response, cell wall integrity and binds Cdc42, a Rho-like small GTP-binding protein required for polarized morphogenesis. We have cloned the STE20 homologue from the fungal pathogen Candida glabrata and have shown that it is present in a single copy in the genome. Translation of the nucleotide sequence predicts that C. glabrata Ste20 contains a highly conserved p21-activated serine-threonine protein kinase domain, a binding site for G-protein beta subunits and a regulatory Rho-binding domain that enables the kinase to interact with Cdc42 and/or Rho-like small GTPases. C. glabrata Ste20 has 53% identity and 58% predicted amino acid similarity to S. cerevisiae Ste20 and can complement both the nitrogen starvation-induced filamentation and mating defects of S. cerevisiae ste20 mutants. Analysis of ste20 null and disrupted strains suggest that in C. glabrata Ste20 is required for a fully functional hypertonic stress response and intact cell wall integrity pathway. C. glabrata Ste20 is not required for nitrogen starvation-induced filamentation. Survival analysis revealed that C. glabrata ste20 mutants, while still able to cause disease, are mildly attenuated for virulence compared to reconstituted STE20 cells.
authors.affiliation: Department of Infectious Diseases, Imperial College London, Du Cane Road, London W12 ONN, UK.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Calcagno
authors.forename: Elaine
authors.initials: E
authors.lastname: Bignell
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Rogers
authors.forename: Mariana
authors.initials: M
authors.lastname: Canedo
authors.forename: Fritz A
authors.initials: FA
authors.lastname: Mühlschlegel
authors.forename: Ken
authors.initials: K
authors.lastname: Haynes
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D041221:Candida glabrata / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology*; D002473:Cell Wall / Q000201:enzymology / Q000502:physiology; D003001:Cloning, Molecular; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D005816:Genetic Complementation Test; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D014774:Virulence
chemical_list: D004271:DNA, Fungal; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D017346:Protein Serine-Threonine Kinases; D020930:MAP Kinase Kinase Kinases; C078754:STE20 protein, S cerevisiae