title: The NDR/LATS kinase Cbk1 controls the activity of the transcriptional regulator Bcr1 during biofilm formation in Candida albicans.
abstract: 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.
authors.affiliation: Departamento Ciencias Biomédicas, Universidad de Extremadura, Badajoz, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Gutiérrez-Escribano
authors.forename: Ute
authors.initials: U
authors.lastname: Zeidler
authors.forename: M Belén
authors.initials: MB
authors.lastname: Suárez
authors.forename: Sophie
authors.initials: S
authors.lastname: Bachellier-Bassi
authors.forename: Andrés
authors.initials: A
authors.lastname: Clemente-Blanco
authors.forename: Julie
authors.initials: J
authors.lastname: Bonhomme
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Vázquez de Aldana
authors.forename: Christophe
authors.initials: C
authors.lastname: d'Enfert
authors.forename: Jaime
authors.initials: J
authors.lastname: Correa-Bordes
mesh_terms: D000818:Animals; D018441:Biofilms / Q000254:growth & development*; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D002177:Candidiasis; D002448:Cell Adhesion / Q000235:genetics; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases