Biofilm matrix regulation by Candida albicans Zap1

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Journal titlePLoS Biology
Pagese1000133-1e1000133-15; # of pages: 15
SubjectBinding Sites; Biofilms; Candida; Candida albicans; Chromatin Immunoprecipitation; Fungal Proteins; Gene Expression Regulation,Fungal; Genes; Genes,Fungal; genetics; genome; growth & development; Human; Humans; Hydrolysis; Immunoprecipitation; In Vitro; metabolism; microbiology; Microscopy,Confocal; Microscopy,Electron,Scanning; pha; physiology; Protein; Proteins; Regulon; Saccharomyces cerevisiae; Vitro
AbstractA 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 β-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 β-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.
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AffiliationNational Research Council Canada (NRC-CNRC); NRC Biotechnology Research Institute
Peer reviewedYes
NRC number50652
NPARC number12921151
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Record identifierd5fa7454-d5f0-49f9-8418-26832b7f9148
Record created2010-06-02
Record modified2016-05-09
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