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Transcriptional comparison of C. albicans WT and ACE2 knockout strains

ABSTRACT: Ace2 transcription factor family genes are found in many fungal genomes and are required for regulation of expression of genes involved in cell separation. We used transcriptional profiling to identify the targets of Ace2 in Candida albicans, and we show that these include several cell wall components, such as glucanases and glycosylphosphatidylinositol-anchored proteins. Expression is downregulated in ace2 deletion mutants in both yeast and hyphal cells. In addition, deleting ace2 results in dramatic changes in expression of metabolic pathways. Expression of glycolytic enzymes is reduced, while expression of respiratory genes (including those involved in the tricarboxylic acid cycle, oxidative phosphorylation, and ATP synthesis) is increased. Similar changes occur in both yeast and hyphal cells. In contrast, genes required for acetyl-coenzyme A and lipid metabolism are upregulated in an ace2 deletion mutant grown predominantly as yeast cells but are downregulated in hyphae. These results suggest that in wild-type strains, Ace2 acts to increase glycolysis and reduce respiration. This is supported by the observation that deleting ace2 results in increased resistance to antimycin A, a drug that inhibits respiration. We also show that Ace2 is required for filamentation in response to low oxygen concentrations (hypoxia). We suggest that filamentation is induced in wild-type cells by reducing respiration (using low oxygen or respiratory drugs) and that mutants with increased respiratory activity fail to undergo filamentation under these conditions. This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Candida albicans

PROVIDER: GSE7105 | GEO | 2007/02/23

SECONDARY ACCESSION(S): PRJNA98437

REPOSITORIES: GEO

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Project description:Deleting components of the Arp2/3 complex in Candida albicans resulted in a global lack of hyphal specific gene induction. This observation suggests that the failure in hyphal growth of Arp2/3 complex mutants could be a result of failure to activate hyphal specific genes. If the hyphal defect was primarily due to failure to activate gene expression, de-repressing hyphal-specific gene expression by deleting the NRG1 repressor could potentially suppress the defect, as deletion of NRG1 leads to constitutive filamentous growth even in the absence of any hyphal induction signals (Garcia-Sanchez et al., 2005, Kadosh & Johnson, 2005). We therefore created an nrg1Î/Îarp2Î/Î mutant. When grown under non-inducing conditions, nrg1Î/Îarp2Î/Î cells showed the arp2Î/Î mutant morphology of round and swollen cells. When induced for hyphal growth, nrg1Î/Îarp2Î/Î cells also exhibited the arp2Î/Î cell morphology and did not form hyphae even after extended overnight incubation times. To determine if the hyphal-specific genes are de-repressed in the nrg1Î/Îarp2Î/Î mutant, we performed transcript profiling. We compared the nrg1Î/Îarp2Î/Î mutant grown under hyphal conditions to the arp2Î/Î mutant grown under the same conditions (10% serum, 37ï°C, three hours), and found that a significant number of hyphal-specific genes that are normally induced when WT cells are undergoing the yeast to hyphae switch (WT-HY) showed greater expression in the nrg1Î/Îarp2Î/Î mutant compared to arp2Î/Î cells (p-value 4.9x10-9). When we examined the set of NRG1-dependent hyphal-specific genes previously identified (Kadosh & Johnson, 2005), we found that seven of 28 genes (HYR1, SAP5, SAP4, KIP4, ORF19.6079, ALS3 and UME6) showed significantly increased expression (â¥ 2 fold) in nrg1Î/Îarp2Î/Î cells compared to arp2Î/Î cells, while a further four genes (IHD1, CBP1, ORF19.6705 and ALS10) showed moderately increased expression between 1.5 and 2-fold. Thus, while deleting a transcriptional repressor of the filamentation program leads to de-repression of many hyphal genes, the entire regulated gene set is not de-repressed; this presumably reflects the complex interplay that different transcriptional (co-) repressors exert on the yeast-to-hyphae transition (Garcia-Sanchez et al., 2005, Kadosh & Johnson, 2005). We further found that despite the increased induction of some hyphal genes in the nrg1Î/Îarp2Î/Î mutant, a few of those genes are not as highly induced as in WT cells. One gene that was induced in both the ânrg1Î/Îarp2Î/Î vs arp2Î/Îâ and the ânrg1Î/Îarp2Î/Î vs WTâ-comparisons is UME6, a recently identified key regulator of the hyphal program (Banerjee et al., 2008, Zeidler et al., 2009). Interestingly, although constitutive over-expression of UME6 in WT cells resulted in constitutive filamentous growth even in the absence of hyphae signals (Carlisle et al., 2009), the increased expression level of UME6 in the nrg1Î/Îarp2Î/Î mutant is not sufficient to restore filamentation in the absence of a functional Arp2/3 complex. Thus despite partial de-repression of the hyphal program, hyphae do not form, making it likely other roles of the Arp2/3 complex, such as its function in actin patch formation and actin branching, are required for hyphal development.

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Transcriptional comparison of C. albicans WT and ACE2 knockout strains

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