Biofilm Matrix Regulation by Candida albicans Zap1

• Published in: PLoS biology Vol. 7; no. 6; p. e1000133
• Main Authors: Nobile, Clarissa J., Nett, Jeniel E., Hernday, Aaron D., Homann, Oliver R., Deneault, Jean-Sebastien, Nantel, Andre, Andes, David R., Johnson, Alexander D., Mitchell, Aaron P.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.06.2009; Public Library of Science (PLoS)
• Subjects: Bacteriology; Binding Sites; Biofilms; Biofilms - growth & development; Candida albicans; Candida albicans - genetics; Candida albicans - physiology; Chromatin Immunoprecipitation; Control; Extracellular matrix; Fungal Proteins - metabolism; Gene Expression Regulation, Fungal; Genes, Fungal; Genetic aspects; Genetics and Genomics/Gene Function; Infections; Infectious Diseases/Fungal Infections; Influence; Microbial mats; Microbiology; Microbiology/Microbial Growth and Development; Microscopy, Confocal; Microscopy, Electron, Scanning; Regulon - genetics; Saccharomyces cerevisiae - genetics; Structure; Transcription factors; United States; Candida albicans; Gene Expression Regulation, Fungal; Regulon; Microscopy, Confocal; Microscopy, Electron, Scanning; Biofilms; Chromatin Immunoprecipitation; Fungal Proteins; Genes, Fungal; Binding Sites; Saccharomyces cerevisiae
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.1000133

A biofilm is a surface-associated population of microorganisms embedded in a matrix of extracellular polymeric substances. Biofilms are a major natural growth form of microorganisms and the cause of pervasive device-associated infection. This report focuses on the biofilm matrix of Candida albicans, the major fungal pathogen of humans. We report here that the C. albicans zinc-response transcription factor Zap1 is a negative regulator of a major matrix component, soluble beta-1,3 glucan, in both in vitro and in vivo biofilm models. To understand the mechanistic relationship between Zap1 and matrix, we identified Zap1 target genes through expression profiling and full genome chromatin immunoprecipitation. On the basis of these results, we designed additional experiments showing that two glucoamylases, Gca1 and Gca2, have positive roles in matrix production and may function through hydrolysis of insoluble beta-1,3 glucan chains. We also show that a group of alcohol dehydrogenases Adh5, Csh1, and Ifd6 have roles in matrix production: Adh5 acts positively, and Csh1 and Ifd6, negatively. We propose that these alcohol dehydrogenases generate quorum-sensing aryl and acyl alcohols that in turn govern multiple events in biofilm maturation. Our findings define a novel regulatory circuit and its mechanism of control of a process central to infection.