title: The lack of upstream elements of the Cek1 and Hog1 mediated pathways leads to a synthetic lethal phenotype upon osmotic stress in Candida albicans.
abstract: Different signal transduction pathways mediated by MAP kinases have been described in Candida albicans. These pathways sense different stimuli and, therefore, elaborate specific responses. Hog1 was identified as the MAPK that is primarily involved in stress response and virulence, while Cek1 was more specific to cell wall biogenesis, mating and biofilm formation. In the present work, mutants defective in both pathways have been characterized under osmotic stress. Both routes are required for a full response against high osmotic challenge, since mutants defective in both pathways displayed aberrant morphology, cell polarity defects and abnormal chitin deposition, which correlate with loss of viability and appearance of apoptotic markers. These alterations occurred in spite of proper Hog1 and Cek1 phosphorylation and increased intra-cellular glycerol accumulation. The relevance of both routes in virulence is shown as ssk1 msb2 sho1 opy2 mutants are avirulent in a mouse systemic model of infection and display reduced virulence in the Galleria mellonella model.
authors.affiliation: Aberdeen Fungal Group, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, United Kingdom(1).
authors.forename: Carmen
authors.initials: C
authors.lastname: Herrero-de-Dios
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, E-28040 Madrid, Spain. Electronic address: realonso@ucm.es.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Alonso-Monge
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, E-28040 Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pla
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D002177:Candidiasis / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D007915:Lepidoptera; D051379:Mice; D050296:Microbial Viability / Q000187:drug effects; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D009997:Osmotic Pressure; D050436:Regulatory Elements, Transcriptional; D017384:Sequence Deletion; D015398:Signal Transduction; D014774:Virulence
chemical_list: D005656:Fungal Proteins; C077339:CEK1 protein, Candida albicans; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases
keywords: Candida albicans; Cek1; Cell wall integrity; HOG pathway; MAPK; Osmotic stress; Pathogenic fungus