Candida albicans
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ABSTRACT:
PROVIDER: PRJNA135635 | ENA |
REPOSITORIES: ENA
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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: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. CLAM-bM-^@M-^Ys 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 CLAM-bM-^@M-^Ys ability to inhibit hyphal growth in C. albicans. Two-color experimental design that consistently used growth in Spider Media at 30M-bM-^DM-^C as the control. We tested the effect of high temperature as well as the effect of adding 100 mM-BM-5 CLA at either low or high temperature. RNA from each replicate came from independent cultures.
2011-03-10 | E-GEOD-25822 | biostudies-arrayexpress
Project description:Candida albicans, the most common cause of human fungal infections, undergoes a reversible morphological transition from yeast to pseudohyphal and hyphal filaments, which is required for virulence. For many years, the relationship between global gene expression patterns associated with determination of specific C. albicans morphologies has remained obscure. Using a strain that can be genetically manipulated to sequentially transition from yeast to pseudohyphae to hyphae in the absence of complex environmental cues and upstream signaling pathways, we demonstrate by whole-genome transcriptional profiling that genes associated with pseudohyphae represent a subset of those associated hyphae and are generally expressed at lower levels; interestingly, no genes appeared to be expressed exclusively in pseudohyphae. Our results also strongly suggest that in addition to dosage, extended duration of filament-specific gene expression is sufficient to drive the C. albicans yeast-pseudohyphal-hyphal transition. Finally, we describe the first transcriptional profile of the C. albicans reverse hyphal-pseudohyphal-yeast transition and demonstrate that this transition not only involves down-regulation of known hyphal-specific genes but also differential expression of additional genes which have not previously been associated with the forward transition, including many involved in protein synthesis. These findings provide new insight into genome-wide mechanisms important for determining fungal morphology and suggest that in addition to similarities, there are also fundamental differences in global gene expression as pathogenic filamentous fungi undergo forward and reverse morphological transitions.
2012-12-12 | GSE39677 | GEO
Project description:Sfl1p and Sfl2p are two homologous heat shock factor-type transcriptional regulators that antagonistically control morphogenesis in Candida albicans, while being required for full pathogenesis and virulence. To understand how Sfl1p and Sfl2p exert their function, we combined genome-wide location and expression analyses to reveal their transcriptional targets in vivo together with the associated changes of the C. albicans transcriptome. We show that Sfl1p and Sfl2p bind to the promoter of at least 113 common targets through divergent binding motifs and modulate directly the expression of key transcriptional regulators of C. albicans morphogenesis and/or virulence. Surprisingly, we found that Sfl2p additionally binds to the promoter of 75 specific targets, including a high proportion of hyphal-specific genes (HSGs; HWP1, HYR1, ECE1, others), revealing a direct link between Sfl2p and hyphal development. Data mining pointed to a regulatory network in which Sfl1p and Sfl2p act as both transcriptional activators and repressors. Sfl1p directly represses the expression of positive regulators of hyphal growth (BRG1, UME6, TEC1, SFL2), while upregulating both yeast form-associated genes (RME1, RHD1,YWP1) and repressors of morphogenesis (SSN6, NRG1). On the other hand, Sfl2p directly upregulates HSGs and activators of hyphal growth (UME6, TEC1), while downregulating yeast form-associated genes and repressors of morphogenesis (NRG1, RFG1, SFL1). Using genetic interaction analyses, we provide further evidences that Sfl1p and Sfl2p antagonistically control C. albicans morphogenesis through direct modulation of the expression of important regulators of hyphal growth. Bioinformatic analyses suggest that binding of Sfl1p and Sfl2p to their targets occurs with the co-binding of Efg1p and/or Ndt80p. Indeed, we show that Sfl1p and Sfl2p targets are bound by Efg1p and that both Sfl1p and Sfl2p associate in vivo with Efg1p. Taken together, our data suggest that Sfl1p and Sfl2p act as central “switch on/off” proteins to coordinate the regulation of C. albicans morphogenesis.
2013-06-15 | GSE42886 | GEO
Project description:Transcriptome analysis of wild type and set3-deficient Candida albicans cells in yeast and hyphal morphological phases
2013-01-01 | GSE38426 | GEO
Project description:Identification of genes differentially expressed in Candida albicans upon hyphal growth
2015-01-01 | GSE54694 | GEO
Project description:Transcriptional profiling of CDC53 down-regulated Candida albicans cells compared to control cells Keywords: comparative genomic hybridization, genetic modification Candida albicans is an important opportunistic human fungal pathogen, which can cause mucosal as well as systemic infections in immunocompromised patients. Critical for the virulence of C. albicans is its ability to undergo a morphological transition from yeast to hyphal growth mode. Proper induction of filamentation is dependent on the ubiquitination pathway, which targets proteins for proteasome-mediated protein degradation or activates them for signaling events. In the present study, we evaluated the role of ubiquitination in C. albicans by impairing the function of the major ubiquitin-ligase complex SCF. This was done by depleting its backbone, the cullin Cdc53p (orf19.1674), using a tetracycline down-regulatable promoter system. Cdc53p-depleted cells displayed an invasive phenotype and constitutive filamentation under conditions favouring yeast growth mode, both on solid and in liquid media. In addition, these cells exhibited an early onset of cell death, as judged from propidium iodide staining, suggesting that CDC53 is an essential gene in C. albicans. To identify Cdc53p-dependent pathways in C. albicans, a genome-wide expression analysis was carried out that revealed a total of 425 differentially expressed genes (fold change ≥ 2, p-value ≤ 0.05) with 192 up- and 233 down-regulated genes in the CDC53-repressed mutant as compared to the control strain. GO term analysis identified biological processes significantly affected by Cdc53p depletion, including amino acid starvation response, with 14 genes being targets of the transcriptional regulator Gcn4p, and reductive iron transport. These results indicate that Cdc53p enables C. albicans to adequately respond to environmental signals.
2009-01-01 | GSE13976 | GEO
Project description:Although Candida albicans and Candida dubliniensis are most closely related, both species significantly behave differently with respect to morphogenesis and virulence. In order to gain further insight into the divergent routes for morphogenetic adaptation in both species, we investigated qualitative along with quantitative differences in the transcriptomes of both organisms by cDNA deep sequencing. Following genome-associated assembly of sequence reads we were able to generate experimentally verified databases containing 6016 and 5972 genes for C. albicans and C. dubliniensis, respectively. About 95% of the transcriptionally active regions (TARs) contain open reading frames while the remaining TARs most likely represent non-coding RNAs. Comparison of our annotations with publically available gene models for C. albicans and C. dubliniensis confirmed approximately 95% of already predicted genes, but also revealed so far unknown novel TARs in both species. Qualitative cross-species analysis of these databases revealed in addition to 5802 orthologs also 399 and 49 species-specific protein coding genes for C. albicans and C. dubliniensis, respectively. Furthermore, quantitative transcriptional profiling using RNA-Seq revealed significant differences in the expression of orthologs across both species. We defined a core subset of 84 hyphal-specific genes required for both species, as well as a set of 42 genes that seem to be specifically induced during hyphal morphogenesis in C. albicans. Species specific adaptation in C. albicans and C. dubliniensis is governed by individual genetic repertoires but also by altered regulation of conserved orthologs on the transcriptional level.
2013-04-17 | GSE41749 | GEO
Project description:Although Candida albicans and Candida dubliniensis are most closely related, both species significantly behave differently with respect to morphogenesis and virulence. In order to gain further insight into the divergent routes for morphogenetic adaptation in both species, we investigated qualitative along with quantitative differences in the transcriptomes of both organisms by cDNA deep sequencing. Following genome-associated assembly of sequence reads we were able to generate experimentally verified databases containing 6016 and 5972 genes for C. albicans and C. dubliniensis, respectively. About 95% of the transcriptionally active regions (TARs) contain open reading frames while the remaining TARs most likely represent non-coding RNAs. Comparison of our annotations with publically available gene models for C. albicans and C. dubliniensis confirmed approximately 95% of already predicted genes, but also revealed so far unknown novel TARs in both species. Qualitative cross-species analysis of these databases revealed in addition to 5802 orthologs also 399 and 49 species-specific protein coding genes for C. albicans and C. dubliniensis, respectively. Furthermore, quantitative transcriptional profiling using RNA-Seq revealed significant differences in the expression of orthologs across both species. We defined a core subset of 84 hyphal-specific genes required for both species, as well as a set of 42 genes that seem to be specifically induced during hyphal morphogenesis in C. albicans. Species specific adaptation in C. albicans and C. dubliniensis is governed by individual genetic repertoires but also by altered regulation of conserved orthologs on the transcriptional level. We investigated qualitative along with quantitative differences in the transcriptomes of both organisms by cDNA deep sequencing. In a first step, we reevaluated the in silico predicted gene models by collecting experimental data using FLX - technology for sequencing strand-specific and normalized cDNA libraries derived from blastospores and hyphae. In the second step, quantitative RNA-Seq (GAIIX) was applied to C. albicans hyphal cells and C. dubliniensis blastospore and hyphal cells to complement reevaluation of the gene models with FLX data as well as to measure differential gene expression across the species with two biological replicates.
2013-04-17 | E-GEOD-41749 | biostudies-arrayexpress