The NDR/LATS kinase Cbk1 controls the activity of the transcriptional regulator Bcr1 during biofilm formation in Candida albicans
Autor: | Ute Zeidler, Christophe d'Enfert, Sophie Bachellier-Bassi, Julie Bonhomme, M. Belén Suárez, Jaime Correa-Bordes, Andrés Clemente-Blanco, Pilar Gutiérrez-Escribano, Carlos R. Vázquez de Aldana |
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Přispěvatelé: | Universidad de Extremadura (UEX), Biologie et Pathogénicité fongiques, Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Universidad de Salamanca, Imperial College London, This work was supported by grants from the Spanish Ministry of Science and Innovation (BFU2009-11251 to J. C.-B. and BFU2010-15884 to C.R.V.) and the Regional Government of Extremadura (PRI08A017, GRU09001 and GRU10008) to J. C.-B. All Spanish funding was co-sponsored by the European Union FEDER programme. P.G-E. was supported by a pre-doctoral fellowship (FPU program) from the Spanish Government. Work in the C. d’E. laboratory was supported by the European Commission (FINSysB, PITN-GA-2008-214004) and Agence Nationale de la Recherche (KANJI, ANR-08-MIE-033-01). U.Z. was a recipient of post-doctoral fellowship of Institut Carnot «Pasteur Maladies Infectieuses» (Programme Fungi). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip, ANR-08-MIEN-0033,KANJI,Colonisation et invasion de la muqueuse digestive par le champignon pathogène de l'homme Candida albicans(2008), European Project: 214004,PEOPLE,FP7-PEOPLE-2007-1-1-ITN,FINSYSB(2008), Universidad de Extremadura - University of Extremadura (UEX), Biologie et Pathogénicité fongiques (BPF), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris], Consejo Superior de Investigaciones Científicas [Spain] (CSIC) |
Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
MESH: Membrane Glycoproteins
Regulator genes ComputingMilieux_LEGALASPECTSOFCOMPUTING biofilm Mice Gene Expression Regulation Fungal transcription d'adn Candida albicans Transcriptional regulation MESH: Animals Biology (General) Phosphorylation [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology gène régulateur Regulation of gene expression 0303 health sciences Fungal protein Mice Inbred BALB C NDR kinase Membrane Glycoproteins biology Candidiasis Intracellular Signaling Peptides and Proteins MESH: Transcription Factors MESH: Gene Expression Regulation MESH: Candidiasis 3. Good health Female MESH: Fungal Proteins MESH: Gene Expression Regulation Fungal expression des gènes Research Article Transcriptional Activation QH301-705.5 Immunology Genes Fungal MESH: Mice Inbred BALB C Saccharomyces cerevisiae MESH: Biofilms Protein Serine-Threonine Kinases Microbiology MESH: Protein-Serine-Threonine Kinases MESH: Cell Adhesion Fungal Proteins 03 medical and health sciences Virology MESH: Intracellular Signaling Peptides and Proteins Genetics Cell Adhesion Transcription factors Animals Molecular Biology Transcription factor Biology MESH: Mice 030304 developmental biology 030306 microbiology MESH: Candida albicans Biofilm réaction en chaîne par polymérase RC581-607 biochemical phenomena metabolism and nutrition biology.organism_classification Gene regulation Gene Expression Regulation Phosphoprotein Biofilms MESH: Transcriptional Activation Parasitology Gene expression Immunologic diseases. Allergy MESH: Genes Fungal facteur de transcription MESH: Female |
Zdroj: | PLoS Pathogens PLoS Pathogens, Public Library of Science, 2012, 8 (5), pp.e1002683. ⟨10.1371/journal.ppat.1002683⟩ PLoS Pathogens, 2012, 8 (5), pp.e1002683. ⟨10.1371/journal.ppat.1002683⟩ Plos Pathogens 5 (8), . (2012) Digital.CSIC. Repositorio Institucional del CSIC instname PLoS Pathogens, Vol 8, Iss 5, p e1002683 (2012) |
ISSN: | 2009-1125 1553-7366 1553-7374 |
Popis: | This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al. In nature, many microorganisms form specialized complex, multicellular, surface-attached communities called biofilms. These communities play critical roles in microbial pathogenesis. The fungal pathogen Candida albicans is associated with catheter-based infections due to its ability to establish biofilms. The transcription factor Bcr1 is a master regulator of C. albicans biofilm development, although the full extent of its regulation remains unknown. Here, we report that Bcr1 is a phosphoprotein that physically interacts with the NDR kinase Cbk1 and undergoes Cbk1-dependent phosphorylation. Mutating the two putative Cbk1 phosphoacceptor residues in Bcr1 to alanine markedly impaired Bcr1 function during biofilm formation and virulence in a mouse model of disseminated candidiasis. Cells lacking Cbk1, or any of its upstream activators, also had reduced biofilm development. Notably, mutating the two putative Cbk1 phosphoacceptor residues in Bcr1 to glutamate in cbk1Δ cells upregulated the transcription of Bcr1-dependent genes and partially rescued the biofilm defects of a cbk1Δ strain. Therefore, our data uncovered a novel role of the NDR/LATS kinase Cbk1 in the regulation of biofilm development through the control of Bcr1. © 2012 Gutiérrez-Escribano et al. This work was supported by grants from the Spanish Ministry of Science and Innovation (BFU2009-11251 to J. C.-B. and BFU2010-15884 to C.R.V.) and the Regional Government of Extremadura (PRI08A017, GRU09001 and GRU10008) to J. C.-B. All Spanish funding was co-sponsored by the European Union FEDER programme. P.G-E. was supported by a pre-doctoral fellowship (FPU program) from the Spanish Government. Work in the C. d’E. laboratory was supported by the European Commission (FINSysB, PITN-GA-2008-214004) and Agence Nationale de la Recherche (KANJI, ANR-08-MIE-033-01). U.Z. was a recipient of post-doctoral fellowship of Institut Carnot «Pasteur Maladies Infectieuses» (Programme Fungi). |
Databáze: | OpenAIRE |
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