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

PLoS Pathogens

Christophe d'Enfert¹  Carlos R. Vázquez de Aldana²  Pilar Gutiérrez-Escribano²  M. Belén Suárez³  Julie Bonhomme³  Ute Zeidler⁴  Andrés Clemente-Blanco⁴  Jaime Correa-Bordes⁴  Sophie Bachellier-Bassi⁵ 

[1] Cell Cycle Group, MRC Clinical Sciences Centre, Imperial College, London, United Kingdom;Departamento Ciencias Biomédicas, Universidad de Extremadura, Badajoz, Spain;INRA, USC2019, Paris, France;Institut Pasteur, Unité Biologie et Pathogénicité Fongiques, Département Génomes et Génétique, Paris, France;Instituto de Biología Funcional y Genómica, CSIC-Universidad de Salamanca, Salamanca, Spain

关键词: Biofilms;    C;    ida albicans;    Phosphorylation;    Transcriptional control;    Gene expression;    Transcription factors;    Saccharomyces cerevisiae;    Gene regulation;   

DOI  :  10.1371/journal.ppat.1002683

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY