C. albicans white-opaque transcription factor binding recorded in the mammalian gut
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ABSTRACT:
ORGANISM(S): Candida albicans
PROVIDER: GSE150856 | GEO | 2020/06/01
REPOSITORIES: GEO
Similar Datasets
Project description:Among ~5,000,000 fungal species on Earth, Candida albicans is exceptional in its lifelong association with humans, where it exists either as a benign component of the gastrointestinal microbiome or as an invasive pathogen. Although it is generally assumed that invasiveness results from a breakdown of host immunity , it is also possible that specific fungal programs control the transition between these divergent lifestyles. Here, we report that exposure of C. albicans to the mammalian gut triggers a developmental switch, driven by the Wor1 transcription factor, to a commensal cell type. Wor1 has been thought to occur only in unique genetic backgrounds, but we show that WOR1 expression is triggered when wild-type cells are propagated in a murine gastrointestinal infection model. Similar to Wor1’s role in a white-opaque switch for mating, WOR1 overexpression within the host induces a novel switch affecting cell and colony morphology and conferring commensal fitness. However, these hyperfit GUT (Gastrointestinally-IndUced Transition) cells lack the functional hallmarks of opaque cells, which they resemble morphologically, whereas bona fide opaque cells are defective for commensalism. Instead, the GUT cell transcriptome is optimized for the environment of the distal mammalian digestive tract. The GUT cell type switch illuminates how a single organism can utilize distinct genetic programs to transition between commensalism and invasive tissue pathogenesis Candida albicans strains including the Wild type strain (SN425), WOR1OE -White (a/a, SN1044), WOR1OE -GUT (a/a, SN1045), White (a/a, SN966) and Opaque (a/a, SN967) were grown at room temperature in SC medium supplemented with 100ug/ml adenine; 2-4 biological replicates were performed per strain. RNA was prepared from these strains and samples were hybridized on custom Agilent C. albicans ORF arrays (15,000 spots/array, 70-mer probes).
2013-07-28 | E-GEOD-43972 | biostudies-arrayexpress
Project description:The ability to undergo heritable switching between cell states is well recognized in microbial species. In the human fungal pathogen Candida albicans, cells can stably exist in several alternative states that show differential interactions with the mammalian host. Here, we demonstrate that gene dosage of the master transcription factor, Efg1, controls access to distinct cell states in diploid C. albicans cells. Thus, cells that are hemizygous for EFG1 can stably differentiate into a cell state that is not available to cells with two functional copies of the EFG1 gene. Strikingly, we reveal that a number of clinical isolates of C. albicans encode polymorphisms that produce a hemizygous EFG1 genotype and that this enables access to the novel cell state. Furthermore, we show that C. albicans cells in different cell states each exhibit unique interactions with the mammalian host, with consequences for both commensalism and pathogenesis.
2019-01-31 | GSE105399 | GEO
Project description:Among ~5,000,000 fungal species on Earth, Candida albicans is exceptional in its lifelong association with humans, where it exists either as a benign component of the gastrointestinal microbiome or as an invasive pathogen. Although it is generally assumed that invasiveness results from a breakdown of host immunity , it is also possible that specific fungal programs control the transition between these divergent lifestyles. Here, we report that exposure of C. albicans to the mammalian gut triggers a developmental switch, driven by the Wor1 transcription factor, to a commensal cell type. Wor1 has been thought to occur only in unique genetic backgrounds, but we show that WOR1 expression is triggered when wild-type cells are propagated in a murine gastrointestinal infection model. Similar to Wor1’s role in a white-opaque switch for mating, WOR1 overexpression within the host induces a novel switch affecting cell and colony morphology and conferring commensal fitness. However, these hyperfit GUT (Gastrointestinally-IndUced Transition) cells lack the functional hallmarks of opaque cells, which they resemble morphologically, whereas bona fide opaque cells are defective for commensalism. Instead, the GUT cell transcriptome is optimized for the environment of the distal mammalian digestive tract. The GUT cell type switch illuminates how a single organism can utilize distinct genetic programs to transition between commensalism and invasive tissue pathogenesis
2013-07-28 | GSE43972 | GEO
Project description:The human pathogen Candida albicans can assume either of two distinct cell types, designated ‘‘white’’ and ‘‘opaque.’’ Each cell type is maintained for many generations; switching between them is rare and stochastic, and occurs without any known changes in the nucleotide sequence of the genome. The two cell types differ dramatically in cell shape, colony appearance, mating competence, and virulence properties. In this work, we investigate the transcriptional circuitry that specifies the two cell types and controls the switching between them. First, we identify two new transcriptional regulators of white-opaque switching, Czf1 and white-opaque regulator 2 (Wor2). Analysis of a large set of double mutants and ectopic expression strains revealed genetic relationships between CZF1, WOR2, and two previously identified regulators of white-opaque switching, WOR1 and EFG1. Using chromatin immunoprecipitation, we show that Wor1 binds the intergenic regions upstream of the genes encoding three additional transcriptional regulators of white-opaque switching (CZF1, EFG1, and WOR2), and also occupies the promoters of numerous white- and opaque-enriched genes. Based on these interactions, we have placed these four genes in a circuit controlling white-opaque switching whose topology is a network of positive feedback loops, with the master regulator gene WOR1 occupying a central position. Our observations indicate that a key role of the interlocking feedback loop network is to stably maintain each epigenetic state through many cell divisions. Keywords: ChIP-chip
2007-10-01 | GSE8709 | GEO
Project description:The goals of this study were to identify the Efg1p-regulon during GI tract colonization and to compare C. albicans gene expression during colonization of different organs of the GI tract. Our results identified significant differences in gene expression between cells colonizing the cecum and ileum. In addition, during laboratory growth, efg1- null mutant cells grew to a higher density than WT cells. The efg1- null mutant grew in depleted medium, while WT cells could only grow if the depleted medium was supplemented with carnitine, a compound that promotes the metabolism of fatty acids. During colonization, efg1- null mutant cells expressed higher levels of genes involved in lipid catabolism, carnitine biosynthesis and carnitine utilization in comparison to colonizing WT cells. This altered gene expression supports the ability of efg1- cells to hypercolonize naïve mice. C. albicans cells (WT, efg1-, efg1- efh1- or efg1- cph1-) were inoculated into antibiotic-treated BALB/c mice by oral gavage. Contents of the cecum and ileum were collected and frozen in RNALater. Reference cells (WT C. albicans) were grown in YPD medium at 37oC to exponential phase. Total RNA was extracted from both all samples. Sample of C. albicans isolated from GI tract organs was compared to reference on microarray. Between 4 and 7 microarray hybridizations, with dye swaps, were performed for each sample.
2013-02-08 | E-GEOD-41771 | biostudies-arrayexpress
Project description:We use ChIP-seq to identify the targets of Efg1 in Candida parapsilosis. We show that Efg1 binds to 502 promoter regions, including 70 potential transcription factors or regulatory proteins. Several of the transcription factors belong to networks that regulate biofilm development and white-opaque switching in C. albicans. Efg1 also binds to its own promoter. The binding site for C. parapsilosis Efg1 resembles that of orthologs in other fungi. Many Efg1 targets are probably also regulated by the Ndt80 transcription factor.
2013-06-20 | GSE41063 | GEO
Project description:The capacity of the commensal yeast Candida albicans to grow in several forms, referred to as phenotypic plasticity, is critical for its survival, and abilities to thrive and cause infection in the human host. In this study, we report a novel phenotype of C. albicans, referred as the “gray” phenotype. The gray cell type, together with the previously discovered “white” and “opaque” cell types, forms a tristable phenotypic switching system. The three phenotypes differ in cellular and colony appearance, global transcriptional profiles, secreted aspartyl proteinase (Sap) activities and virulence in different infection models. The addition of the gray cell type to the phenotypic transition systems may enhance fitness and confers an adaptive advantage for C. albicans in the host. We further demonstrate that two key regulators of white-opaque switching, Wor1 and Efg1, are not required for maintenance of the gray phenotype, suggesting that a different regulatory circuitry may be involved in the regulation of gray cell formation. Our study provides an example of multiple stable and heritable switching systems, indicating that the regulation of morphological forms to adapt to environmental changes could be much more elaborate than previously thought.
2014-06-30 | GSE53671 | GEO
Project description:The capacity of the commensal yeast Candida albicans to grow in several forms, referred to as phenotypic plasticity, is critical for its survival, and abilities to thrive and cause infection in the human host. In this study, we report a novel phenotype of C. albicans, referred as the “gray” phenotype. The gray cell type, together with the previously discovered “white” and “opaque” cell types, forms a tristable phenotypic switching system. The three phenotypes differ in cellular and colony appearance, global transcriptional profiles, secreted aspartyl proteinase (Sap) activities and virulence in different infection models. The addition of the gray cell type to the phenotypic transition systems may enhance fitness and confers an adaptive advantage for C. albicans in the host. We further demonstrate that two key regulators of white-opaque switching, Wor1 and Efg1, are not required for maintenance of the gray phenotype, suggesting that a different regulatory circuitry may be involved in the regulation of gray cell formation. Our study provides an example of multiple stable and heritable switching systems, indicating that the regulation of morphological forms to adapt to environmental changes could be much more elaborate than previously thought. total RNA profiles of 24h old white, gray and opaque cell types
2014-06-30 | E-GEOD-53671 | biostudies-arrayexpress
Project description:We use ChIP-seq to identify the targets of Efg1 in Candida parapsilosis. We show that Efg1 binds to 502 promoter regions, including 70 potential transcription factors or regulatory proteins. Several of the transcription factors belong to networks that regulate biofilm development and white-opaque switching in C. albicans. Efg1 also binds to its own promoter. The binding site for C. parapsilosis Efg1 resembles that of orthologs in other fungi. Many Efg1 targets are probably also regulated by the Ndt80 transcription factor. Efg1 in C. parapsilosis was tagged in situ using a myc epitope. Examination of Efg1-myc DNA binding sites by ChIP-seq. Three immunoprecipitated samples were sequenced and three input samples (pre-immunoprecipitation) were sequenced as controls.
2013-06-20 | E-GEOD-41063 | biostudies-arrayexpress
Project description:In Candida albicans the Efg1 transcription factor (a member of the APSES family) is an important regulator of hyphal growth, and of the white-to-opaque transition. In contrast, we show that the Efg1 ortholog in Candida parapsilosis is a major regulator of a different morphological switch at the colony level, from a concentric to smooth morphology. The rate of switching is at least 100-fold increased in an efg1 knockout relative to wild type. Deleting efg1 also reduces biofilm formation, and results in increased sensitivity to SDS, Congo red, caspofungin and calcofluor white in cells of both morphologies. Biofilm reduction is more dramatic in in vitro than in in vivo models. We use ChIP-seq to show that Efg1 binds to 502 promoter regions, including 70 potential transcription factors or regulatory proteins. Several of the transcription factors belong to networks that regulate biofilm development and white-opaque switching in C. albicans. Efg1 also binds to its own promoter. The binding site for C. parapsilosis Efg1 resembles that of orthologs in other fungi. Many Efg1 targets are probably also regulated by the Ndt80 transcription factor. We show that a paralog of Efg1 (Efh1) is restricted to Candida species. Efh1 does not regulate concentric-smooth phenotype switching, biofilm formation or stress response in C. parapsilosis. Our analysis supports the hypothesis that Efg1 has an ancient role as regulator of development in fungi, but we have identified a new role in C. parapsilosis as a regulator of colony switching that is distinct from the white-opaque switch in C. albicans.
2013-06-20 | GSE41064 | GEO