title: Candida glabrata Ste11 is involved in adaptation to hypertonic stress, maintenance of wild-type levels of filamentation and plays a role in virulence.
abstract: The conserved family of fungal Ste11 mitogen activated protein kinase/kinases play important roles in several signalling cascades. We have cloned the STE11 homologue from the fungal pathogen Candida glabrata. The C. glabrata gene is present in a single copy in the genome, contains a well-conserved catalytic domain typical of the serine-threonine protein kinases and a sterile alpha motif widespread in signalling and nuclear proteins. Hypothetical translation of C. glabrata STE11 suggests that the protein has 64% identity and 77% similarity at the amino acid level to Saccharomyces cerevisiae Ste11. We have shown that C. glabrata STE11 can complement the mating defect and partially rescue the reduced nitrogen starvation induced filamentation of S. cerevisiae ste11 mutants. Functional analysis of a C. glabrata ste11 null mutant demonstrates that Ste11 is required for adaptation to hypertonic stress but is largely dispensable for maintenance of cell wall integrity. It also plays a role in C. glabrata nitrogen starvation induced filamentation. Survival analysis revealed that C. glabrata ste11 mutants, while still able to cause disease, are attenuated for virulence compared to reconstituted, STE11 cells. These data suggest that C. glabrata Ste11, in a similar fashion to the S. cerevisiae protein, functions in a number of different signalling modules.
authors.affiliation: Department of Infectious Diseases, Imperial College London, London, 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: Michael D
authors.initials: MD
authors.lastname: Jones
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; D041221:Candida glabrata / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D018869:Heat-Shock Response; D020930:MAP Kinase Kinase Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D029701:Saccharomyces cerevisiae Proteins; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D020930:MAP Kinase Kinase Kinases; C067018:Ste11 protein, S cerevisiae