The NDR/LATS Kinase Cbk1 Controls the Activity of the Transcriptional Regulator Bcr1 during Biofilm Formation in Candida albicans

• DOI: 10.1371/journal.ppat.1002683
• Publication Date: 2012-05-10T21:10:30Z
• Authors: Pilar Gutiérrez-E...; Ute Zeidler; M. Belén Suárez; Sophie Bachellier...; Andrés Clemente-B...; Julie Bonhomme; Carlos R. Vázquez...; Christophe d'Enfert; Jaime Correa-Bordes
• Keywords: 0301 basic medicine; MESH: Membrane Glycoproteins; Regulator genes; biofilm; Mice; Gene Expression Regulation, Fungal; transcription d'adn; Candida albicans; MESH: Animals; Phosphorylation; Biology (General); Inbred BALB C; [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology; gène régulateur; Mice, Inbred BALB C; 0303 health sciences; Membrane Glycoproteins; phosphorylation; Candidiasis; Intracellular Signaling Peptides and Proteins; MESH: Transcription Factors; MESH: Gene Expression Regulation; MESH: Genes; MESH: Candidiasis; 3. Good health; Fungal; MESH: Fungal Proteins; Female; MESH: Gene Expression Regulation, Fungal; expression des gènes; Research Article; Transcriptional Activation; 570; QH301-705.5; Genes, Fungal; MESH: Mice, Inbred BALB C; 610; MESH: Biofilms; Saccharomyces cerevisiae; Protein Serine-Threonine Kinases; MESH: Protein-Serine-Threonine Kinases; MESH: Cell Adhesion; Fungal Proteins; 03 medical and health sciences; MESH: Intracellular Signaling Peptides and Proteins; Transcription factors; Cell Adhesion; Animals; MESH: Mice; MESH: Candida albicans; réaction en chaîne par polymérase; RC581-607; [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology; Gene regulation; Gene Expression Regulation; Biofilms; MESH: Transcriptional Activation; candida albicans; Gene expression; Immunologic diseases. Allergy; MESH: Genes, Fungal; MESH: Female; facteur de transcription; Transcription Factors

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.