Functional control of the Candida albicans cell wall by catalytic protein kinase A subunit Tpk1

  1. Get@NRC: Functional control of the Candida albicans cell wall by catalytic protein kinase A subunit Tpk1 (Opens in a new window)
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Journal titleMolecular Microbiology
Pages284302; # of pages: 19
Subjectcaspofungin; cell protein; cell surface protein; cyclic AMP dependent protein kinase catalytic subunit; protein Als1; protein Als2; protein Als4; protein Csh1; protein Csp37; protein Tpk1; unclassified drug; antibiotic sensitivity; article; bacterial cell wall; bacterium adherence; biofilm; Candida albicans; cell adhesion; cell wall; controlled study; gene expression; gene function; gene identification; gene repression; genetic epistasis; genetic regulation; homozygosity; nonhuman; nucleotide sequence; priority journal; repressor gene; Tpk1 gene; transcription regulation; Biofilms; Candida albicans; Cell Wall; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; Fungal Proteins; Gene Expression Regulation, Fungal; Candida albicans
AbstractThe cyclic AMP protein kinase A pathway governs numerous biological features of the fungal pathogen Candida albicans. The catalytic protein kinase A subunits, Tpk1 (orf19.4892) and Tpk2 (orf19.2277), have divergent roles, and most studies indicate a more pronounced role for Tpk2. Here we dissect two Tpk1-responsive properties: adherence and cell wall integrity. Homozygous tpk1/tpk1 mutants are hyperadherent, and a Tpk1 defect enables biofilm formation in the absence of Bcr1, a transcriptional regulator of biofilm adhesins. A quantitative gene expression-based assay reveals that tpk1/tpk1 and bcr1/bcr1 genotypes show mixed epistasis, as expected if Tpk1 and Bcr1 act mainly in distinct pathways. Overexpression of individual Tpk1-repressed genes indicates that cell surface proteins Als1, Als2, Als4, Csh1 and Csp37 contribute to Tpk1-regulated adherence. Tpk1 is also required for cell wall integrity, but has no role in the gene expression response to cell wall inhibition by caspofungin. Interestingly, increased expression of the adhesin gene ALS2 confers a cell wall defect, as manifested in hypersensitivity to the cell wall inhibitor caspofungin and a shallow cell wall structure. Our findings indicate that Tpk1 governs C.albicans cell wall properties through repression of select cell surface protein genes. © 2012 Blackwell Publishing Ltd.
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AffiliationNational Research Council Canada (NRC-CNRC); NRC Biotechnology Research Institute (BRI-IRB)
Peer reviewedYes
NPARC number21269450
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Record identifier4f631e31-c6f2-4352-914e-b1a2949e42d4
Record created2013-12-12
Record modified2016-06-01
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