title: Surface stress induces a conserved cell wall stress response in the pathogenic fungus Candida albicans.
abstract: The human fungal pathogen Candida albicans can grow at temperatures of up to 45°C. Here, we show that at 42°C substantially less biomass was formed than at 37°C. The cells also became more sensitive to wall-perturbing compounds, and the wall chitin levels increased, changes that are indicative of wall stress. Quantitative mass spectrometry of the wall proteome using (15)N metabolically labeled wall proteins as internal standards revealed that at 42°C the levels of the β-glucan transglycosylases Phr1 and Phr2, the predicted chitin transglycosylases Crh11 and Utr2, and the wall maintenance protein Ecm33 increased. Consistent with our previous results for fluconazole stress, this suggests that a wall-remodeling response is mounted to relieve wall stress. Thermal stress as well as different wall and membrane stressors led to an increased phosphorylation of the mitogen-activated protein (MAP) kinase Mkc1, suggesting activation of the cell wall integrity (CWI) pathway. Furthermore, all wall and membrane stresses tested resulted in diminished cell separation. This was accompanied by decreased secretion of the major chitinase Cht3 and the endoglucanase Eng1 into the medium. Consistent with this, cht3 cells showed a similar phenotype. When treated with exogenous chitinase, cell clusters both from stressed cells and mutant strains were dispersed, underlining the importance of Cht3 for cell separation. We propose that surface stresses lead to a conserved cell wall remodeling response that is mainly governed by Mkc1 and is characterized by chitin reinforcement of the wall and the expression of remedial wall remodeling enzymes.
authors.affiliation: Department of Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Clemens J
authors.initials: CJ
authors.lastname: Heilmann
authors.forename: Alice G
authors.initials: AG
authors.lastname: Sorgo
authors.forename: Sepehr
authors.initials: S
authors.lastname: Mohammadi
authors.forename: Grazyna J
authors.initials: GJ
authors.lastname: Sosinska
authors.forename: Chris G
authors.initials: CG
authors.lastname: de Koster
authors.forename: Stanley
authors.initials: S
authors.lastname: Brul
authors.forename: Leo J
authors.initials: LJ
authors.lastname: de Koning
authors.forename: Frans M
authors.initials: FM
authors.lastname: Klis
mesh_terms: D002176:Candida albicans / Q000166:cytology / Q000502:physiology*; D002473:Cell Wall / Q000378:metabolism*; D002686:Chitin / Q000378:metabolism; D002688:Chitinases / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D055786:Gene Knockout Techniques; D004693:Glucan Endo-1,3-beta-D-Glucosidase / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D005656:Fungal Proteins; D008562:Membrane Glycoproteins; C091515:PHR1 protein, Candida albicans; D020543:Proteome; D002686:Chitin; C092603:MKC1 protein, Candida albicans; D020928:Mitogen-Activated Protein Kinases; D002688:Chitinases; D004693:Glucan Endo-1,3-beta-D-Glucosidase