title: Proteomic changes associated with inactivation of the Candida glabrata ACE2 virulence-moderating gene.
abstract: Inactivation of the gene encoding the transcriptional activator Ace2 in the fungal pathogen Candida glabrata results in an almost 200-fold increase in virulence characterised by acute mortality and a massive over-stimulation of the pro-inflammatory arm of the innate immune system. In this study we have adopted a proteomics approach to identify cellular functions regulated by C. glabrata Ace2 that might contribute to this increase in virulence. A two-dimensional polyacrylamide gel electrophoresis map of the C. glabrata proteome was constructed. We identified a total of 123 proteins, 61 of which displayed reproducible and statistically significant alterations in their levels following inactivation of ACE2. Of these, the levels of 32 proteins were elevated, and 29 were reduced in ace2 cells. These data show that Ace2 influences metabolism, protein synthesis, folding and targeting, and aspects of cell growth and polarisation. Some of these functions are likely to contribute to the effects of Ace2 upon the virulence of C. glabrata.
authors.affiliation: COGEME Proteomics Research Facility 1, Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, UK.
authors.forename: David
authors.initials: D
authors.lastname: Stead
authors.forename: Helen
authors.initials: H
authors.lastname: Findon
authors.forename: Zhikang
authors.initials: Z
authors.lastname: Yin
authors.forename: Janet
authors.initials: J
authors.lastname: Walker
authors.forename: Laura
authors.initials: L
authors.lastname: Selway
authors.forename: Philip
authors.initials: P
authors.lastname: Cash
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Dujon
authors.forename: Christophe
authors.initials: C
authors.lastname: Hennequin
authors.forename: Alistair J P
authors.initials: AJ
authors.lastname: Brown
authors.forename: Ken
authors.initials: K
authors.lastname: Haynes
mesh_terms: D041221:Candida glabrata / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity*; D015180:Electrophoresis, Gel, Two-Dimensional; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D020868:Gene Silencing; D005800:Genes, Fungal; D006593:Hexokinase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D009154:Mutation; D040901:Proteomics; D014774:Virulence / Q000235:genetics
chemical_list: C505770:ACE2 protein, Candida glabrata; D005656:Fungal Proteins; D007527:Isoenzymes; D006593:Hexokinase