WT vs. ACE2 knockout (grown in hyphal form)
Ontology highlight
ABSTRACT:
ORGANISM(S): Candida albicans
PROVIDER: GSE7100 | GEO | 2007/02/23
SECONDARY ACCESSION(S): PRJNA104147
REPOSITORIES: GEO
Similar Datasets
Project description:We have used DNA microarray technology to compare the expression of over 6000 genes between C. albicans WT and ACE2 knockout strains in the yeast form. Keywords: Gene expression comparison
2007-02-23 | GSE7099 | GEO
Project description: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.
2007-02-23 | GSE7105 | GEO
Project description:The Regulation of Ace2 and Morphogenesis (RAM) pathway is an important regulatory network in the human fungal pathogen Candida albicans. The RAM pathway’s two most well-studied components, the NDR/Lats kinase Cbk1 and its putative substrate, the transcription factor Ace2, have a wide range of phenotypes and functions. It is not clear, however, which of these functions are specifically due to the phosphorylation of Ace2 by Cbk1. To address this question, we first compared the transcriptional profiles of CBK1 and ACE2 deletion mutants. This analysis indicates that, of the large number of genes whose expression is affected by deletion of CBK1 and ACE2, only 5.5% of those genes are concordantly regulated. Our data also suggest that Ace2 directly or indirectly represses a large set of genes during hyphal morphogenesis. Second, we generated strains containing ACE2 alleles with alanine mutations at the Cbk1 phosphorylation sites. Phenotypic and transcriptional analysis of these ace2 mutants indicates that, as in Saccharomyces cerevisiae, Cbk1 regulation is important for daughter cell localization of Ace2 and cell separation during yeast phase growth. In contrast, Cbk1 phosphorylation of Ace2 plays a minor role in C. albicans yeast-to-hyphae transition. We have, however, discovered a new function for the Cbk1-Ace2 axis. Specifically, Cbk1 phosphorylation of Ace2 prevents the hyphae-to-yeast transition. To our knowledge, this is one of the first regulators of the C. albicans hyphae-to-yeast transition to be described. Finally, we present an integrated model for the role of Cbk1 in the regulation of hyphal morphogenesis in C. albicans.
2020-08-26 | GSE155450 | GEO
Project description:Our genetic screen reveals that deletion of CTM1, which abolishes the lysine trimethylation of cytochrome c (Cyc1), results in inhibition of hyphal morphogenesis in Candida albicans. Similar results are observed in the unmethylatable Cyc1 mutant (cyc1K79A). To elucidate how unmethylated Cyc1 inhibits hyphal growth, we performed RNA-Seq analysis by comparing WT (BWP17), ctm1∆/∆, and cyc1K79A cells grown in yeast and hyphal condition. Consistent with previous published data, many hyphal specific genes (HSGs), such as ALS3, ECE1, HWP1, and UME6, are upregulated while three major hyphal suppressor genes, TUP1, NRG1, and RFG1, are downregulated when WT cells switch from yeast to hyphal growth. Similar changes are observed in ctm1Δ/Δ and cyc1K79A cells upon hyphal induction, even though most mutant cells maintain yeast morphology throughout the induction. Further comparisons reveal that the basal transcriptional levels of HSGs are much lower in ctm1Δ/Δ and cyc1K79A cells than those in WT cells. Upon hyphal induction, the levels of HSGs in ctm1Δ/Δ and cyc1K79A cells increase but still remain lower than their basal levels in WT cells. In contrast, the hyphal suppressor genes (especially NRG1) exhibit much higher basal transcriptional levels in ctm1Δ/Δ and cyc1K79A cells than in WT cells. Their transcriptional levels reduce upon hyphal induction but still remain higher than the basal levels in WT cells. Together, these data suggest that unmethylated Cyc1 inhibits hyphal morphogenesis via transcriptional regulation of HSGs and hyphal suppressor genes.
2024-01-01 | GSE243813 | GEO
Project description:The polymorphic yeast Candida albicans exists in blastospore and filamentous forms. The switch from one morphological state to the other coincides with the expression of virulence factors, which makes the yeast-to-hypha transition an attractive target for the development of new antifungal agents. Because an untapped therapeutic potential resides in small molecules that hinder C. albicans filamentation, we characterized the inhibitory effect of conjugated linoleic acid (CLA) on hyphal growth and addressed its mechanism of action. CLA inhibited hyphal growth in a dose-dependent fashion, in both liquid- and solid-inducing media. The fatty acid blocked germ tube formation and impeded hyphal elongation. Global transcriptional profiling revealed that CLA downregulated the expression of hypha-specific genes and abrogated the induction of several morphogenesis regulators, including RAS1, TEC1 and UME6. CLA’s repressive effect on TEC1 expression was Ras1-dependent, but Efg1-independent. CLA treatment resulted in the delocalization of Ras1 and its degradation, resulting in the downregulation of the Ras1-cAMP-PKA signaling pathway. This study provides the biological and molecular explanations that underlie CLA’s ability to inhibit hyphal growth in C. albicans.
2011-03-10 | GSE25822 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE19565: Arp2/3 complex mutants show a pronounced lack of hyphal specific gene expression in Candida albicans GSE19582: Partial de-repression of the hyphal program does not restore hyphae formation in absence of a functional Arp2/3 complex Refer to individual Series
2010-05-15 | E-GEOD-19583 | biostudies-arrayexpress
Project description:Whole cell lysates from yeast or hyphal Candida albicans cells were obtained and proteins were analysed by MS in order to have a global view of proteome differences between both fungal morphologies. This analysis constitute an interesting approach to decipher proteomic differences underlying morphological switch intimately related to Candida albicans virulence. A total of 811 different proteins were identified from hyphal whole cell lysates and 976 from yeast whole cell lysates. In terms of biological significance, we only took into consideration proteins that were identified in at least two biological replicates with at least two peptides and a q-value< 0.01.
2021-09-13 | PXD021504 | Pride
Project description:Candida albicans is a diploid fungal pathogen lacking a defined complete sexual cycle, and thus has been refractory to standard forward genetic analysis. Instead, transcription profiling and reverse genetic strategies based on Saccharomyces cerevisiae have typically been used to link genes to functions. To overcome restrictions inherent in such indirect approaches, we have investigated a forward genetic mutagenesis strategy based on the UAU1 technology. We screened 4700 random insertion mutants for defects in hyphal development, and linked two new genes (ARP2 and VPS52) to hyphal growth. Deleting ARP2 abolished hyphal formation, generated round and swollen yeast phase cells, disrupted cortical actin patches and blocked virulence in mice. The mutants also showed a global lack of induction of hyphae-specific genes upon the yeast-to-hyphae switch. Surprisingly, both arp2Î/Î and arp2Î/Îarp3Î/Î mutants were still able to endocytose FM4-64 and Lucifer Yellow, although as shown by time-lapse movies internalization of FM4-64 was somewhat delayed in mutant cells. Thus the non-essential role of the Arp2/3 complex discovered by forward genetic screening in C. albicans showed that uptake of membrane components from the plasma membrane to vacuolar structures is not dependent on this actin nucleating machinery. By forward genetic screening, we have identified genes that are essential for hyphal formation. One of the hits is the Arp2/3 complex, which is essential for hyphal formation, but not for viability in Candida albicans. To gain insights into cellular processes affected by disrupting Arp2/3 complex functions, we performed transcriptional profiling under yeast growth conditions (YPD at 30°C for three hours) or hyphal induction (YPD + 10% FBS at 37°C for three hours) and compared transcriptional consequences of deleting ARP2 to MYO5 and SLA2 microarray data sets (Oberholzer et al., 2006).
2010-10-08 | E-GEOD-19565 | biostudies-arrayexpress
Project description:The homologous Ace2 and Swi5 transcription factors of Saccharomyces cerevisiae have identical DNA-binding domains, and both are cell cycle regulated. There are common target genes, as well as genes activated only by Ace2 and other genes activated only by Swi5. Keywords: genetic modification RNA was isolated from four strains: wild type, ace2 gene deletion, swi5 gene deletion, and the ace2 swi5 double gene deletion. RNAs from the three mutant strains were compared to wild type RNA in a microarray hybridization experiment.
2008-05-13 | E-GEOD-11380 | biostudies-arrayexpress
Project description:Candida albicans is an opportunistic pathogenic fungus that is able to assume several morphologies, including yeast and hyphal growth forms. The hyphal morphology can be induced by various environmental stimuli and is accompanied by expression of a large set of hyphal-specific genes (HSGs). Cell cycle and morphogenetic programs are interconnected: notably, inhibition of cell cycle progression often causes a switch to filamentous growth. Here we identify and characterize CaNrm1, a C. albicans homolog of the S. cerevisiae Whi5 and Nrm1 transcription inhibitors that, analogous to mammalian Rb, regulate the cell cycle transcription program in the G1 phase and at the G1/S transition. CaNRM1 is able to complement the phenotypes of both whi5 and nrm1 mutants in S. cerevisiae. Deletion of CaNRM1 causes a reduction in cell size and results in increased resistance to hydroxyurea (HU), an inhibitor of DNA replication; analysis of the expression of ribonucleotide reductase, the target of HU, suggests that its transcriptional induction in response to HU is mainly dependent upon CaNrm1. Genetic epistasis analysis suggests that CaNrm1 interacts with the SBF and MBF transcription factors in S. cerevisiae and with the MBF functional homolog in C. albicans. At the transcription level, deletion of CaNRM1 causes an induction of many G1 and G1/S-specific genes. Induction of the HSGs is dampened under certain conditions in the Canrm1-/- mutant, suggesting that the cell cycle transcription program influences the morphogenetic transcription program of C. albicans.
2012-01-01 | GSE20612 | GEO