Bypass of Candida albicans Filamentation/Biofilm Regulators through Diminished Expression of Protein Kinase Cak1

• Published in: PLoS genetics Vol. 12; no. 12; p. e1006487
• Main Authors: Woolford, Carol A, Lagree, Katherine, Xu, Wenjie, Aleynikov, Tatyana, Adhikari, Hema, Sanchez, Hiram, Cullen, Paul J, Lanni, Frederick, Andes, David R, Mitchell, Aaron P
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-12-2016; Public Library of Science (PLoS)
• Subjects: Biofilms; Biofilms - growth & development; Biology and Life Sciences; Candida albicans; Candida albicans - genetics; Candida albicans - growth & development; Candidiasis - genetics; Candidiasis - microbiology; Cell cycle; Cell Cycle - genetics; Cell growth; Colleges & universities; Cyclin-Dependent Kinases - genetics; Cytoskeleton - genetics; Funding; Fungal Proteins - biosynthesis; Fungal Proteins - genetics; Gene expression; Gene Expression Regulation, Fungal; Humans; Hyphae - genetics; Hyphae - growth & development; Hyphae - pathogenicity; Immunology; Infections; Kinases; Medical equipment; Medicine and Health Sciences; Morphogenesis - genetics; Protein Kinases - biosynthesis; Protein Kinases - genetics; Proteins; Research and Analysis Methods; Transcription factors; Transcription Factors - biosynthesis; Transcription Factors - genetics; New York; Pittsburgh Pennsylvania; United States > US; Wisconsin; Pennsylvania
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1006487

Biofilm formation on implanted medical devices is a major source of lethal invasive infection by Candida albicans. Filamentous growth of this fungus is tied to biofilm formation because many filamentation-associated genes are required for surface adherence. Cell cycle or cell growth defects can induce filamentation, but we have limited information about the coupling between filamentation and filamentation-associated gene expression after cell cycle/cell growth inhibition. Here we identified the CDK activating protein kinase Cak1 as a determinant of filamentation and filamentation-associated gene expression through a screen of mutations that diminish expression of protein kinase-related genes implicated in cell cycle/cell growth control. A cak1 diminished expression (DX) strain displays filamentous growth and expresses filamentation-associated genes in the absence of typical inducing signals. In a wild-type background, expression of filamentation-associated genes depends upon the transcription factors Bcr1, Brg1, Efg1, Tec1, and Ume6. In the cak1 DX background, the dependence of filamentation-associated gene expression on each transcription factor is substantially relieved. The unexpected bypass of filamentation-associated gene expression activators has the functional consequence of enabling biofilm formation in the absence of Bcr1, Brg1, Tec1, Ume6, or in the absence of both Brg1 and Ume6. It also enables filamentous cell morphogenesis, though not biofilm formation, in the absence of Efg1. Because these transcription factors are known to have shared target genes, we suggest that cell cycle/cell growth limitation leads to activation of several transcription factors, thus relieving dependence on any one.