The Candida albicans regulator ZCF21 controls the expression of cell wall components
Ontology highlight
ABSTRACT:
ORGANISM(S): Candida albicans
PROVIDER: GSE73373 | GEO | 2015/11/01
SECONDARY ACCESSION(S): PRJNA296818
REPOSITORIES: GEO
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Project description:We report that a transcriptional regulator that originated in the lineage that gave rise to multiple host-associated Candida species is a key component of the circuitry that governs the C. albicans cell surface composition. Specifically, we show that the transcription regulator ZCF21 controls the expression of genes encoding multiple cell surface proteins and cell wall modifying enzymes. Transcriptome (RNA-seq) analysis of 2 Candida albicans strains (reference strain and zcf21 deletion mutant) grown under 4 culture conditions (YPD broth at 30°C for 24h; YPD broth at 30°C in the presence of 15 mM caffeine for 24h; Todd-Hewitt agar at 37°C for 24h; Todd-Hewitt agar at 37°C for 24h in the presence of 5 mM caffeine).
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Project description:The cyclic AMP-protein kinase A pathway has a central role in the biology of Candida albicans, a prominent fungal pathogen of humans. The two catalytic subunits for cyclic AMP-dependent protein kinase, 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 central transcriptional regulator of biofilm adhesins. Microarray analysis revealed an enrichment for cell wall and surface functions among Tpk1-repressed genes, and overexpression of individual target 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 cell wall integrity gene expression response. Interestingly, increased expression of the adhesin gene ALS2 conferred 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 has a central role in C. albicans cell wall properties that is exerted through repression of select cell surface protein genes.
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Project description:The cyclic AMP-protein kinase A pathway has a central role in the biology of Candida albicans, a prominent fungal pathogen of humans. The two catalytic subunits for cyclic AMP-dependent protein kinase, 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 central transcriptional regulator of biofilm adhesins. Microarray analysis revealed an enrichment for cell wall and surface functions among Tpk1-repressed genes, and overexpression of individual target 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 cell wall integrity gene expression response. Interestingly, increased expression of the adhesin gene ALS2 conferred 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 has a central role in C. albicans cell wall properties that is exerted through repression of select cell surface protein genes. Two-color microarrays using a closed-loop experimental design to determine the effects of a M-bM-^HM-^Ftpk1 deletion in the absence or presence of the antifungal Caspofungin (CF)
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