Transcriptome analysis uncovers a link between copper metabolism, and both fungal fitness and antifungal sensitivity in the opportunistic yeast Candida albicans
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ABSTRACT:
ORGANISM(S): Candida albicans
PROVIDER: GSE147697 | GEO | 2020/03/30
REPOSITORIES: GEO
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Project description:Copper homeostasis is an important determinant for virulence of many human pathogenic fungi such as the highly prevalent yeast Candida albicans. However, beyond the copper transporter Ctr1, little is known regarding other genes and biological processes that are affected by copper. To gain insight into the cellular processes that are modulated by copper abundance in C. albicans, we monitored the global gene expression dynamic under both copper depletion and excess using RNA-seq. Beyond copper metabolism, other different transcriptional programs related to fungal fitness such as stress responses, antifungal sensitivity, host invasion and commensalism were modulated in response to copper variations. We have also investigated the transcriptome of the mutant of the copper utilization regulator, mac1, and identified potential direct targets of this transcription factor under copper starvation. We also showed that Mac1 was required for the invasion and adhesion to host cells and antifungal tolerance. This study provides a framework for future studies to examine the link between copper metabolism and essential functions that modulate fungal virulence and fitness inside the host.
| S-EPMC7248230 | biostudies-literature
Project description:Transcriptome analysis uncovers a link between copper metabolism, and both fungal fitness and antifungal sensitivity in the opportunistic yeast Candida albicans
| PRJNA616132 | ENA
Project description:To identify genes in that are misregulated in the grf10Δ mutant of Candida albicans in response to growth in high copper, we compared expression patterns of the grf10-null mutant relative to the isogenic WT in YPD medium supplemented with and without 12 mM CuSO4.
2023-03-20 | GSE223217 | GEO
Project description:Copper is both an essential metal for life, but is also toxic at high concentrations. In mammalian cells, two copper transporters are known, one localized at the plasma membrane (CTR1) and one localized in late endosomes-lysosomes (CTR2). In order to gain insights on the possible influence of the importing pathway on cellular responses to copper, two copper challenges were compared, one with copper ion, which is likely to use preferentially CTR1, and one with a copper-polyacrylate complex, which will likely to be internalized via the endosomal pathway and therefore use preferentially CTR2. A model system consisting in the J774A1 mouse macrophage system, with a strong endosomal/lysosomal pathway, was used. In order to gain wide insights into the cellular responses to copper, a two-dimensional gel-based proteomic approach was used. The proteomic results were validated by targeted experiments, and showed differential effects of the import mode on general cellular physiology parameters such as the reduced glutathione content, the actin cytoskeleton or the mitochondrial potential, but also on more specialized macrophage functions such as phagocytosis or inflammatory responses.
2024-07-08 | PXD021252 | Pride
Project description:Given the risk of Candida albicans overgrowth in the gut, novel complementary therapies should be developed to reduce fungal dominancy. This study highlights the antifungal characteristics of a Bacillus subtilis-derived secondary metabolite, surfactin with high potential against C. albicans. Surfactin inhibited the growth of C. albicans following a 1-hour exposure, in addition to reduced adhesion and morphogenesis. Specifically, surfactin did not affect the level of reactive oxygen species but increased the level of reduced glutathione. Surprisingly, ethanol production was increased following 2 hours of surfactin exposure. Surfactin treatment caused a significant reduction in intracellular iron, manganese and zinc content compared to control cells, whereas the level of copper was not affected. Alongside these physiological properties, surfactin also enhanced fluconazole efficacy. To gain detailed insights into the surfactin-related effects on C. albicans, genome-wide gene transcription analysis was performed. Surfactin treatment resulted in 1390 differentially expressed genes according to total transcriptome sequencing (RNA-Seq). Of these, 773 and 617 genes with at least a 1.5-fold increase or decrease in transcription, respectively, were selected for detailed investigation. Several genes involved in morphogenesis or related to metabolism (e.g., glycolysis, ethanol and fatty acid biosynthesis) were down-regulated. Moreover, surfactin decreased the expression of ERG1, ERG3, ERG9, ERG10 and ERG11 involved in ergosterol synthesis, whereas genes associated with ribosome biogenesis and iron metabolism and drug transport-related genes were up-regulated. Our data demonstrate that surfactin significantly influences the physiology and gene transcription of C. albicans, and could contribute to the development of a novel innovative complementary therapy.
2022-06-02 | GSE199383 | GEO
Project description:In an approach to generate Saccharomyces cerevisiae strains with increased intracellular copper amounts for technical applications we over-expressed the copper transporter CTR1 and a variant of CTR1 with a truncation in the C-terminus after the 300 amino acids (CTR1 delta-300). We determined the copper sensitivity of the generated strains and used inductively coupled plasma spectrometry (ICP-OES and ICP-MS) analysis to investigate the effects of over-expression of both constructs under excess copper on the cellular content of different elements in S. cerevisiae. In addition, we ran DNA microarray analysis to obtain the gene expression profile under the changed element contents. Over-expression of CTR1 increased the copper content in the cells up to 160% and 78 genes were differentially regulated. Over-expression of the truncated CTR1 delta-300 resulted in an increased copper, iron and zinc content of more than 200% and 980 genes showed differential expression. We found that transition metal ion homeostasis was disrupted in CTR1 delta-300 over-expressing strains under excess copper and that this was combined with a transcriptional remodelling of cellular processes
2014-01-28 | GSE44043 | GEO
Project description:The effect of the heavy metal copper on the expression of a wide spectrum of genes was analyzed by using a DNA microarray. Gene expression profile of baker’s yeast Saccharomyces cerevisiae grown in a media containing sub-lethal concentration of cupric sulfate was compared with those of yeast grown in a normal media. Among about 6200 ORFs of yeast, 143 ORFs were induced more than two-fold to resist against copper toxicity after exposure to copper. As was expected, FRE1, FRE7, and CTR1, genes controlled by Mac1p, were strongly down-regulated. Copper metallothionein CUP1-1 and CUP1-2 were induced more than 20-fold. Some genes related to sulfur metabolism and oxidative stress response were also up-regulated. This DNA microarray technology indicated that plasma membrane, cell wall, protein, and DNA, were molecular targets of copper toxicity. Keywords: stress response
2007-11-01 | GSE9231 | GEO
Project description:In Saccharomyces cerevisiae, copper ions regulate gene expression through the two transcriptional activators, Ace1 and Mac1. Ace1 mediates Cu-induced gene expression in cells exposed to stressful levels of copper salts, whereas Mac1 activates a subset of genes under copper-deficient conditions. DNA microarray hybridization experiments revealed a limited set of yeast genes differentially expressed under growth conditions of excess copper or copper deficiency. Mac1 activates the expression of six S. cerevisiae genes, including CTR1, CTR3, FRE1, FRE7, YJL217w and YFR055w. Two of the last three newly identified Mac1 target genes have no known function, the third, YFR055w, is homologous to cystathionine gamma-lyase encoded by CYS3. Several genes that are differentially expressed in cells containing a constitutively active Mac1, designated Mac1up1, are not direct targets of Mac1. Induction or repression of these genes is likely a secondary effect of cells due to constitutive Mac1 activity. Elevated copper levels induced the expression of the metallothioneins CUP1 and CRS5, and two genes, FET3 and FTR1, in the iron uptake system. Cu-induced FET3 and FTR1 expression arises from an indirect Cu effect on cellular Fe pools. This study is described in more detail in Gross C et al.(2000) J Biol Chem 275:32310-6 Keywords: other
2002-02-12 | GSE26 | GEO
Project description:In an approach to generate Saccharomyces cerevisiae strains with increased intracellular copper amounts for technical applications we over-expressed the copper transporter CTR1 and a variant of CTR1 with a truncation in the C-terminus after the 300 amino acids (CTR1 delta-300). We determined the copper sensitivity of the generated strains and used inductively coupled plasma spectrometry (ICP-OES and ICP-MS) analysis to investigate the effects of over-expression of both constructs under excess copper on the cellular content of different elements in S. cerevisiae. In addition, we ran DNA microarray analysis to obtain the gene expression profile under the changed element contents. Over-expression of CTR1 increased the copper content in the cells up to 160% and 78 genes were differentially regulated. Over-expression of the truncated CTR1 delta-300 resulted in an increased copper, iron and zinc content of more than 200% and 980 genes showed differential expression. We found that transition metal ion homeostasis was disrupted in CTR1 delta-300 over-expressing strains under excess copper and that this was combined with a transcriptional remodelling of cellular processes Transcription profiling was performed in Saccharomyces cerevisiae BY4741 (referred to as wild type) over-expressing CTR1 and in the ctr1- deletion strain BY4741 delta-ctr1 overexpressing CTR1 delta-300 after 7 hours of culture under excess copper (0.02 mM CuCl2). Control strains contained the corresponding empty vector. Three independent experiments were performed and 12 samples were analyzed.
2014-01-28 | E-GEOD-44043 | biostudies-arrayexpress
Project description:Human serum amyloid A (SAA) is a major acute phase protein and shows a massive increase of concentration in plasma during inflammation. In the current study, we report that recombinant human and mouse SAA1 (rhSAA1 and rmSAA1) have a potent antifungal activity against the major fungal pathogen Candida albicans. rhSAA1 binds to the cell surface of C. albicans and promotes cell aggregation. At high concentrations, rhSAA1 disrupts the membrane integrity and induces rapid cell death of C. albicans. Further investigation demonstrates that rhSAA1 targets on the cell wall adhesin Als3 of C. albicans. Inactivation of ALS3 in C. albicans leads to remarkably decreased cell aggregation and death upon rhSAA1 treatment, implying that Als3 plays a critical role in SAA1 sensing. Moreover, deletion of the ALS3 transcriptional regulators such as AHR1, BCR1, and EFG1 in C. albicans results in a similar effect on cell responses to that of the als3/als3 mutant upon rhSAA1 treatment. Global gene expression profiling analysis indicates that rhSAA1 has a remarkable impact on the expression of cell wall- and metabolism-related genes in C. albicans. Our finding of the antifungal activity of rhSAA1 against C. albicans expands the function of this protein and would provide new insights into the understanding of the host-Candida interaction during infections.
2019-09-01 | GSE128598 | GEO