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PROVIDER: PRJNA144561 | ENA |
REPOSITORIES: ENA
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Project description:A unique iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis [ChIP_chip]
| PRJNA154667 | ENA
Project description:A unique iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis [Expression Array]
| PRJNA154669 | ENA
Project description:The mammalian gastrointestinal tract and the bloodstream are highly disparate biological niches, and yet certain commensal-pathogenic microorganisms are able to thrive in both environments. Here, we report the evolution of a unique transcription circuit in the yeast, Candida albicans, which determines its fitness in both host niches. Our comprehensive analysis of the DNA-binding proteins that regulate iron uptake by this organism suggests the evolutionary intercalation of a transcriptional activator called Sef1 between two broadly conserved transcriptional repressors, Sfu1 and Hap43. The Sef1 activator of iron uptake genes promotes virulence in a mouse model of bloodstream infection, whereas the Sfu1 repressor is dispensable for virulence but promotes gastrointestinal commensalism. We propose that the ability to alternate between genetic programs conferring resistance to iron depletion in the bloodstream versus iron toxicity in the gut may be a fundamental attribute of gastrointestinal commensal-pathogens.
2011-07-13 | GSE30591 | GEO
Project description:The mammalian gastrointestinal tract and the bloodstream are highly disparate biological niches, and yet certain commensal-pathogenic microorganisms are able to thrive in both environments. Here, we report the evolution of a unique transcription circuit in the yeast, Candida albicans, which determines its fitness in both host niches. Our comprehensive analysis of the DNA-binding proteins that regulate iron uptake by this organism suggests the evolutionary intercalation of a transcriptional activator called Sef1 between two broadly conserved transcriptional repressors, Sfu1 and Hap43. The Sef1 activator of iron uptake genes promotes virulence in a mouse model of bloodstream infection, whereas the Sfu1 repressor is dispensable for virulence but promotes gastrointestinal commensalism. We propose that the ability to alternate between genetic programs conferring resistance to iron depletion in the bloodstream versus iron toxicity in the gut may be a fundamental attribute of gastrointestinal commensal-pathogens.
2011-07-13 | GSE30590 | GEO
Project description:The mammalian gastrointestinal tract and the bloodstream are highly disparate biological niches, and yet certain commensal-pathogenic microorganisms are able to thrive in both environments. Here, we report the evolution of a unique transcription circuit in the yeast, Candida albicans, which determines its fitness in both host niches. Our comprehensive analysis of the DNA-binding proteins that regulate iron uptake by this organism suggests the evolutionary intercalation of a transcriptional activator called Sef1 between two broadly conserved transcriptional repressors, Sfu1 and Hap43. The Sef1 activator of iron uptake genes promotes virulence in a mouse model of bloodstream infection, whereas the Sfu1 repressor is dispensable for virulence but promotes gastrointestinal commensalism. We propose that the ability to alternate between genetic programs conferring resistance to iron depletion in the bloodstream versus iron toxicity in the gut may be a fundamental attribute of gastrointestinal commensal-pathogens. ChIP analyses to profile genome-wide of distribution of Sef1, Sfu1 and Hap43 in response to various iron availability. 12 independent ChIP experiments were performed on 6 biological replicates of the untagged control and 2 biological replicates each of Sef1-Myc, Sfu1-Myc, and Hap43-Myc.
2011-07-12 | E-GEOD-30591 | 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 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:Candida species is a common fungus that had evolved as both commensal and opportunistic pathogen in humans. The rise in human morbidity and mortality caused by Candida species sparked an alarming concern. However, the thin line between commensalism and infection as well as the analysis of Candida host-pathogen interactions has not been completely elucidated prior to the birth of global gene expression technologies. Gene expression analysis of host response upon systemic candidiasis had been carried out using Beadarray and validated by using GenomeLab™ GeXP multiplex PCR. Whole blood from infected mouse was isolated, globin mRNA depleted through subtractive hybridization and its RNA purified. Results from microarray data demonstrated increased expression of genes involved in the pathogen recognition, signal transduction, inflammation, microbial killing and in antigen processing. Interestingly, we also discovered possible increment of erythropoiesis in our animal model and this lead us to believe that Candida tropicalis might possess potent haemolytic factors to sequester iron from the host erythrocytes. Taken together, our data also suggest novel genes such as syndecans and dendritic cell immunoreceptor which might be exploited by Candida tropicalis in its pathogenesis in the host. Nevertheless, the challenge ahead is to understand the specific roles of these genes that underlies in Candida tropicalis pathogenesis.
2010-12-31 | GSE16339 | GEO
Project description:Candida species is a common fungus that had evolved as both commensal and opportunistic pathogen in humans. The rise in human morbidity and mortality caused by Candida species sparked an alarming concern. However, the thin line between commensalism and infection as well as the analysis of Candida host-pathogen interactions has not been completely elucidated prior to the birth of global gene expression technologies. Gene expression analysis of host response upon systemic candidiasis had been carried out using Beadarray and validated by using GenomeLab™ GeXP multiplex PCR. Whole blood from infected mouse was isolated, globin mRNA depleted through subtractive hybridization and its RNA purified. Results from microarray data demonstrated increased expression of genes involved in the pathogen recognition, signal transduction, inflammation, microbial killing and in antigen processing. Interestingly, we also discovered possible increment of erythropoiesis in our animal model and this lead us to believe that Candida tropicalis might possess potent haemolytic factors to sequester iron from the host erythrocytes. Taken together, our data also suggest novel genes such as syndecans and dendritic cell immunoreceptor which might be exploited by Candida tropicalis in its pathogenesis in the host. Nevertheless, the challenge ahead is to understand the specific roles of these genes that underlies in Candida tropicalis pathogenesis. For gene expression analysis, BALB/c mice (six-week-old female weighing 20-25g) were used and the animals were randomized, assigned to the control, sublethal infection and lethal infection groups. At the time of killing, mice were anesthetized and exsanguinated by cardiac puncture. Approximately 200 µl of whole blood was collected and added into 2 ml tubes preloaded with RNAlater (Sigma-Aldrich CO, USA) and stored in -80 °C.
2010-12-31 | E-GEOD-16339 | biostudies-arrayexpress