Gene expression in human fungal pathogen Coccidioides immitis changes as mycelia differentiate into spherules and mature
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ABSTRACT:
ORGANISM(S): Coccidioides immitis RS
PROVIDER: GSE44225 | GEO | 2013/07/11
SECONDARY ACCESSION(S): PRJNA189205
REPOSITORIES: GEO
Similar Datasets
Project description:Coccidioides immitis (C. immitis) is a dimorphic fungus that causes disease in mammals including human beings. It grows as a mycelium in the soil but differentiates into a pathogenic structure called a spherule in the host. We compared the transcriptome of C. immitis mycelia and day 2 and day 8 spherules grown in vitro using a custom custom oligonucleotide microarray from Nimblegen. C. immitis RS strain isolated from infected mice was grown on agar. Arthroconidia was harvested and inoculated into mycelial spores. RNA was extracted from spores at different days post-inoculation and hybridized to a custom Nimblegen array, in order to identify differentially expressed genes between mycelia and spherules.
2013-07-11 | E-GEOD-44225 | biostudies-arrayexpress
Project description:Coccidioides immitis and posadasii are dimorphic fungi that transform from mycelia with internal arthroconidia in the soil to a tissue form known as a spherule. Genes that were highly up-regulated in young spherules include a spherule surface protein and iron and copper membrane transporters. Genes that are unique to Coccidioides spp. are also over-represented in this group, suggesting that they may be important for spherule differentiation. Enriched GO terms in up-regulated genes in young spherules include oxidation/reduction, response to stress and membrane proteins. Down-regulated genes are enriched for transcription factors, especially helix-loop-helix and C2H2 type zinc finger domain-containing proteins which is consistent with the dramatic change in transcriptional profile. Almost all genes that are up-regulated in young spherules remain up-regulated in mature spherules, but a small number of genes are differentially expressed in those two stages of spherule development. Mature spherules express more Hsp31, and amylase than young spherules and less tyrosinase. Some expression of transposons was detected and most of the differentially expressed transposons were up-regulated in spherules.
2021-04-01 | GSE171286 | GEO
Project description:Transcriptional analysis of Coccidioides immitis mycelia and spherules by RNA sequencing
| PRJNA718949 | ENA
Project description:Gene expression in human fungal pathogen Coccidioides immitis changes as mycelia differentiate into spherules and mature
| PRJNA189205 | ENA
Project description:Coccidioidomycosis (Valley Fever) is an emerging endemic fungal infection with a rising incidence and an expanding geographic range. It is caused by Coccidiodes, which are thermally dimorphic fungi that grow as mycelia in soil but transition in the lung to form pathogenic spherules. The regulatory mechanisms underlying this transition are not understood. Exploiting capped small (cs)RNA-seq, which identifies actively initiated stable and unstable transcripts and thereby detects acute changes in gene regulation with remarkable sensitivity, here we report the changes in architectural organization and key sequence features underlying phase transition of this highly pathogenic fungus. Spherule transition was accompanied by large-scale transcriptional reprogramming, functional changes in transcript isoforms, and a massive increase in promoter-distal transcription of ncRNAs. Analysis of spherule-activated regulatory elements revealed a motif predicted to recruit a WOPR family transcription factor, which are known regulators of virulence in other fungi. We identify CIMG_02671 as a C. immitis WOPR homologue and show that it activates transcription in a WOPR motif-dependent manner, suggesting it is an important regulator of pathogenic phase transition. Collectively, this also highlights csRNA-seq as a powerful means to identify transcriptional mechanisms that control pathogenesis.
2022-01-05 | GSE179468 | GEO
Project description:Coccidioides spp. are highly understudied but significant dimorphic fungal pathogens that can infect both immunocompetent and immunocompromised people. In the environment, they grow as multicellular filaments (hyphae) that produce vegetative spores called arthroconidia. Upon inhalation by mammals, arthroconidia undergo a process called spherulation. They enlarge and undergo numerous nuclear divisions to form a spherical structure, and then internally segment until the spherule is filled with multiple cells called endospores. Mature spherules rupture and release endospores, each of which can form another spherule, in a process thought to facilitate dissemination. Spherulation is unique to Coccidioides and its molecular determinants remain largely unknown. Here, we report the first high-density transcriptomic analyses of Coccidioides development, defining morphology-dependent transcripts and those whose expression is regulated by Ryp1, a major regulator required for spherulation and virulence. Of approximately 9000 predicted transcripts, we discovered 273 transcripts with consistent spherule-associated expression, 82 of which are RYP1-dependent, a set likely to be critical for Coccidioides virulence. ChIP-Seq revealed 2 distinct regulons of Ryp1, one shared between hyphae and spherules and the other unique to spherules. Spherulation regulation was elaborate, with the majority of 227 predicted transcription factors in Coccidioides displaying spherule-enriched expression. We identified provocative targets, including 20 transcripts whose expression is endospore-enriched and 14 putative secreted effectors whose expression is spherule-enriched, of which 6 are secreted proteases. To highlight the utility of these data, we selected a cluster of RYP1-regulated, arthroconidia-associated transcripts and found that they play a role in arthroconidia cell wall biology, demonstrating the power of this resource in illuminating Coccidioides biology and virulence.
2024-10-21 | GSE279421 | GEO
Project description:Coccidioides spp. are highly understudied but significant dimorphic fungal pathogens that can infect both immunocompetent and immunocompromised people. In the environment, they grow as multicellular filaments (hyphae) that produce vegetative spores called arthroconidia. Upon inhalation by mammals, arthroconidia undergo a process called spherulation. They enlarge and undergo numerous nuclear divisions to form a spherical structure, and then internally segment until the spherule is filled with multiple cells called endospores. Mature spherules rupture and release endospores, each of which can form another spherule, in a process thought to facilitate dissemination. Spherulation is unique to Coccidioides and its molecular determinants remain largely unknown. Here, we report the first high-density transcriptomic analyses of Coccidioides development, defining morphology-dependent transcripts and those whose expression is regulated by Ryp1, a major regulator required for spherulation and virulence. Of approximately 9000 predicted transcripts, we discovered 273 transcripts with consistent spherule-associated expression, 82 of which are RYP1-dependent, a set likely to be critical for Coccidioides virulence. ChIP-Seq revealed 2 distinct regulons of Ryp1, one shared between hyphae and spherules and the other unique to spherules. Spherulation regulation was elaborate, with the majority of 227 predicted transcription factors in Coccidioides displaying spherule-enriched expression. We identified provocative targets, including 20 transcripts whose expression is endospore-enriched and 14 putative secreted effectors whose expression is spherule-enriched, of which 6 are secreted proteases. To highlight the utility of these data, we selected a cluster of RYP1-regulated, arthroconidia-associated transcripts and found that they play a role in arthroconidia cell wall biology, demonstrating the power of this resource in illuminating Coccidioides biology and virulence.
2024-10-21 | GSE279406 | GEO
Project description:Coccidioides spp. are fungal pathogens endemic to Southern California, Arizona, and other desert regions where they cause a spectrum of symptoms known as Valley Fever in otherwise healthy individuals. In the soil, Coccidioides grows in a hyphal form that produces vegetative spores (arthroconidia). When arthroconidia are inhaled by mammals they undergo an elaborate developmental transition consisting of germination, multiple rounds of nuclear division, and segmentation to form large spherules filled with vegetative endospores. Very little is understood about the molecular basis of spherule formation. Here we characterize the role of the conserved transcription factor Ryp1 in Coccidioides spherule formation. We show that Coccidioides ryp1 mutants are unable to form mature spherules, instead arresting at an early stage of spherulation. We analyze the transcriptional profile of wild-type and Δryp1 mutant cells under hyphal and spherule-promoting conditions, thereby defining a set of hyphal- or spherule-enriched transcripts that are dependent on Ryp1 for their expression. Ryp1-dependent transcripts include key virulence factors such as SOWgp, which encodes the spherule outer wall glycoprotein. In the mouse model of coccidioidomycosis, we find that the Δryp1 mutant is completely avirulent, indicating that Ryp1-dependent pathways are essential for the ability of Coccidioides to cause disease. Vaccination of C57BL/6 mice with live Δryp1 spores does not provide any protection from lethal C. posadasii intranasal infection, consistent with our findings that the Δryp1 mutant fails to make mature spherules. Taken together, this work identifies the first transcriptional regulator that drives mature spherulation and virulence in Coccidioides.
2022-03-03 | GSE178277 | GEO
Project description:Valley fever (coccidioidomycosis) is an endemic fungal pneumonia of the North and South American deserts. The causative agents of Valley fever are the dimorphic fungi Coccidioides immitis and C. posadasii, which grow as mycelia in the environment and spherules within the lungs of vulnerable hosts. The current diagnostics for Valley fever are severely lacking due to poor sensitivity and invasiveness, contributing to a 23-day median time-to-diagnosis, and therefore new diagnostic tools are needed. We are working toward the development of a breath-based diagnostic for coccidioidomycosis, and in this initial study we characterized the volatile metabolomes (or volatilomes) of in vitro cultures of Coccidioides. Using solid-phase microextraction and comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC–TOFMS), we characterized the VOCs produced by six strains of each species during mycelial or spherule growth. We detected a total of 353 VOCs that were at least two-fold more abundant in a Coccidioides culture versus medium controls and found the volatile metabolome of Coccidioides is more dependent on growth phase (spherule versus mycelia) than on the species. The volatile profiles of C. immitis and C. posadasii have strong similarities, indicating that a single suite of Valley fever breath biomarkers can be developed to detect both species.
2021-01-22 | ST001659 | MetabolomicsWorkbench