Time course gene expression profile of YPD medium grown Candida albicans mss11 mutant
Ontology highlight
ABSTRACT:
ORGANISM(S): Candida albicans
PROVIDER: GSE51168 | GEO | 2016/09/24
SECONDARY ACCESSION(S): PRJNA221543
REPOSITORIES: GEO
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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:Candida albicans is an opportunist pathogen responsible for a large spectrum of infections, from superficial mycosis to the systemic disease candidiasis. Its ability to adopt various morphological forms, such as unicellular yeasts, filamentous pseudohyphae and hyphae, contributes to its ability to survive within the host. It has been suggested that the antioxidant glutathione is involved in the filamentation process. We investigated S-glutathionylation, the reversible binding of glutathione to proteins, and the functional consequences on C. albicans metabolic remodeling during the yeast-to-hyphae transition. Our work provided evidence for the specific glutathionylation of mitochondrial proteins involved in bioenergetics pathways in filamentous forms and a regulation of the main enzyme of the glyoxylate cycle, isocitrate lyase, by glutathionylation. Our proteomic data demonstrate that the binding of one glutathione molecule to isocitrate lyase in the hyphal forms leads to enzyme inactivation which was reversed by glutaredoxin treatment. We also assessed the effect of alternative carbon sources on glutathione levels and isocitrate lyase activity. Changes in nutrient availability led to morphological flexibility and was related to perturbations in glutathione levels and isocitrate lyase activity, confirming the key role of the maintenance of intracellular redox status in the adaptive metabolic strategy of the pathogen.
2016-04-21 | PXD003685 | Pride
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. The Dosage Experiment (13 arrays) was performed twice (two biological replicates). MBY38 cells were treated with various concentrations of Doxycycline (Dox): 20 (n=3), 0.4 (n=1), 0.35 (n=1), 0.3 (n=1), 0.25 (n=1), 0.2 (n=1), 0.15 (n=1), 0.1 (n=1), 0.05 (n=1), 0.02 (n=1) and 0 µg/mL (n=1). Each 20 ug/ml sample was used for 3 technical replicate arrays, one of which was labeled using reverse fluors. The reference sample consisted of equal aliquots of the experimental samples. The Forward Transition Experiment (23 arrays) was performed twice (two biological replicates). MBY38 cells were grown in the presence (n=10) or absence (n=10) of 1.0 ug/ml Dox and subsequently harvested at time points between 1 and 10 hours. Each 1.0 ug/mL Dox treated sample was collected at 0 hours and used for 3 technical replicate arrays, one of which was labeled using reverse fluors. The reference sample consisted of equal aliquots of all 21 experimental samples. The Reverse Transition Experiment (26 arrays) was performed twice (two biological replicates). MBY38 cells were grown in the presence (n=10) or absence (n=10) of 20.0 ug/ml Dox and subsequently harvested at time points between 1 and 10 hours. Each 20.0 ug/mL sample was collected at 0 hours and used for 3 technical replicate arrays, one of which was labeled using reverse fluors. Each untreated (no Dox) sample was collected at 0 hours and used for 3 technical replicate arrays, one of which was labeled using reverse fluors. The reference sample consisted of equal aliquots of all 22 experimental samples. The Dox Control Experiment consisted of 12 arrays. PCY87 cells were grown in the presence (n=5) or absence (n=5) of 20.0 ug/ml Dox overnight to create 5 pairs of biological replicates. Three pairs of biological replicates were labelled normally (one of which was repeated as a technical replicate using reverse fluors) and 2 pairs of biological replicates were labeled using reverse fluors. The Dosage Experiment reference was used as the reference sample.
2012-12-12 | E-GEOD-39677 | biostudies-arrayexpress
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:We investigated the roles of mitochondrial dynamics in hyphal growth of C. albicans using the small molecule inhibitor MDIVI-1. Strikingly, the small molecule inhibitor represses both the yeast-to hyphae transition and ongoing filamentation, and its effects on morphogenesis can be uncoupled from general growth inhibition. RNAseq experiments of inhibitor-treated cells coupled with Candida mutant analyses suggest the existence of a novel mechanism of action to represses hyphal growth. The inhibitor was protective to host cells, increasing the survival of bone-marrow derived macrophages in ex vivo macrophage-Candida infection assays, suggesting it has potential as a therapeutic.
2018-11-20 | GSE105148 | GEO
Project description:Comparison of Candida albicans SC5314 treated with fludioxonil for 30 min and untreated controls under hyphae-inducing conditions
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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:Identification of genes differentially expressed in Candida albicans upon hyphal growth
2015-01-01 | GSE54694 | 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: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 nrg1Δ/Δarp2Δ/Δ mutant. When grown under non-inducing conditions, nrg1Δ/Δarp2Δ/Δ cells showed the arp2Δ/Δ mutant morphology of round and swollen cells. When induced for hyphal growth, nrg1Δ/Δarp2Δ/Δ cells also exhibited the arp2Δ/Δ cell morphology and did not form hyphae even after extended overnight incubation times.
2010-01-23 | GSE19582 | GEO