Comparative host transcriptome in response to pathogenic fungi identifies common and species-specific transcriptional antifungal host response pathways
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ABSTRACT:
PROVIDER: PRJNA682949 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13207000.fastq.gz | Fastqsanger.gz | |||
| SRR13207001.fastq.gz | Fastqsanger.gz | |||
| SRR13207002.fastq.gz | Fastqsanger.gz | |||
| SRR13207003.fastq.gz | Fastqsanger.gz | |||
| SRR13207004.fastq.gz | Fastqsanger.gz |
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Project description:Candidiasis, aspergillosis, and mucormycosis cause the majority of nosocomial fungal infections in immunocompromised patients. Using an unbiased transcriptional profiling in PBMCs exposed to the fungal species causing these infections, we found a core host response in healthy individuals that governs effective fungal clearance: it consists of 156 transcripts, involving canonical and non-canonical immune pathways. Systematic investigation of key steps in antifungal host defense revealed fungal-specific signatures. As previously demonstrated, C. albicans induced interferon-related pathways. In contrast, PRRs, ROS production and host glycolytic pathways were down-regulated in response to R. oryzae, and their modulation is associated with ER-stress response. TLR5 was surprisingly identified to be uniquely regulated by A. fumigatus and to control its-induced cytokine release. In conclusion, our data reveals the transcriptional profiles induced by C. albicans, A. fumigatus, and R. oryzae, and describes both the common and specific antifungal host responses that could be exploited for novel therapeutic strategies.
2021-01-31 | GSE162746 | GEO
Project description:Candidiasis, aspergillosis, and mucormycosis cause the majority of nosocomial fungal infections in immunocompromised patients. Using an unbiased transcriptional profiling in PBMCs exposed to the fungal species causing these infections, we found a core host response in healthy individuals that may govern effective fungal clearance: it consists of 156 transcripts, involving canonical and non-canonical immune pathways. Systematic investigation of key steps in antifungal host defense revealed fungal-specific signatures. As previously demonstrated, Candida albicans induced type I and Type II interferon-related pathways. In contrast, central pattern recognition receptor, reactive oxygen species production, and host glycolytic pathways were down-regulated in response to Rhizopus oryzae, which was associated with an ER-stress response. TLR5 was identified to be uniquely regulated by Aspergillus fumigatus and to control cytokine release in response to this fungus. In conclusion, our data reveals the transcriptional profiles induced by C. albicans, A. fumigatus, and R. oryzae, and describes both the common and specific antifungal host responses that could be exploited for novel therapeutic strategies.
| S-EPMC7817431 | biostudies-literature
Project description:The identification of novel transcription factors associated to antifungal response may allow the discovery of fungal specific targets for new therapeutic strategies. A collection of 241 C. albicans transcriptional regulators mutants was screened for altered susceptibility to fluconazole, caspofungin, amphotericin B, and 5-fluorocytosine. Thirteen of these mutants not yet identified in their role in antifungal response were further investigated, and the function of one of them, mutant for orf19.6102 (RCA1) was characterized by transcriptome analysis. Strand specific RNA sequencing and phenotypic tests assigned Rca1 as the regulator of hyphal formation through the cAMP/PKA signaling pathway and the transcription factor Efg1, but also probably through its interaction with a transcriptional repressor, most likely Tup1. The mechanisms responsible for the high level of resistance to caspofungin and fluconazole observed resulting from Rca1 deletion were investigated. From our observations, we propose that caspofungin resistance was the consequence of the deregulation of cell wall gene expression, and that fluconazole resistance was linked to the modulation of the cAMP/PKA signaling pathway activity. In conclusion, our large-scale screening of a C. albicans transcription factor mutants collection allowed the identification of new effectors of the response to antifungals. The functional characterization of Rca1 assigned this TF and its downstream targets as promising candidates for the development of new therapeutic strategies, as Rca1 influences host sensing, hyphal development, and antifungal response. Total RNAs from RCA1 mutant and revertant isolates were extracted in duplicate from exponential growth-phase cultures in YEPD media. Differential expression was resolved by strand specific RNA sequencing.
2012-05-02 | E-GEOD-37682 | biostudies-arrayexpress
Project description:The identification of novel transcription factors associated to antifungal response may allow the discovery of fungal specific targets for new therapeutic strategies. A collection of 241 C. albicans transcriptional regulators mutants was screened for altered susceptibility to fluconazole, caspofungin, amphotericin B, and 5-fluorocytosine. Thirteen of these mutants not yet identified in their role in antifungal response were further investigated, and the function of one of them, mutant for orf19.6102 (RCA1) was characterized by transcriptome analysis. Strand specific RNA sequencing and phenotypic tests assigned Rca1 as the regulator of hyphal formation through the cAMP/PKA signaling pathway and the transcription factor Efg1, but also probably through its interaction with a transcriptional repressor, most likely Tup1. The mechanisms responsible for the high level of resistance to caspofungin and fluconazole observed resulting from Rca1 deletion were investigated. From our observations, we propose that caspofungin resistance was the consequence of the deregulation of cell wall gene expression, and that fluconazole resistance was linked to the modulation of the cAMP/PKA signaling pathway activity. In conclusion, our large-scale screening of a C. albicans transcription factor mutants collection allowed the identification of new effectors of the response to antifungals. The functional characterization of Rca1 assigned this TF and its downstream targets as promising candidates for the development of new therapeutic strategies, as Rca1 influences host sensing, hyphal development, and antifungal response.
2012-05-02 | GSE37682 | GEO
Project description:Gene expression response to the antifungal compound sampangine
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Project description:Fungal infections cause more than 1.5 million deaths a year. Due to emerging antifungal drug resistance, novel strategies are urgently needed to combat life-threatening fungal diseases. Here, we identify the host defense peptide mimetic, brilacidin (BRI) as a synergizer with caspofungin (CAS) against CAS-sensitive and CAS-resistant isolates of Aspergillus fumigatus, Candida albicans, C. auris, and CAS-intrinsically resistant Cryptococcus neoformans. BRI also potentiates azoles against A. fumigatus and several Mucorales fungi. BRI acts in A. fumigatus by affecting cell wall integrity pathway and cell membrane potential. BRI combined with CAS significantly clears A. fumigatus lung infection in an immunosuppressed murine model of invasive pulmonary aspergillosis. BRI alone also decreases A. fumigatus fungal burden and ablates disease development in a murine model of fungal keratitis. Our results indicate that combinations of BRI and antifungal drugs in clinical use are likely to improve the treatment outcome of aspergillosis and other fungal infections.
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Project description:Using a comparative RNA-Sequencing based transcriptional profiling approach, responses of primary human peripheral blood mononuclear cells (PBMCs) to common human pathogenic fungi have been characterized (Bruno et al. Computational and Structural Biology Journal). Primary human PBMCs were stimulated in vitro with the fungi A. fumigatus, C. albicans, and R. oryzae after which RNA was isolated and sequenced. From raw sequencing reads differential expressed genes in response to the different fungi where calculated by comparison with unstimulated cells. By overlapping differentially expressed genes in response to the pathogenic fungi A. fumigatus, C. albicans, and R. oryzae a dataset was generated that encompasses a common response to these three distinct fungi as well as species-specific responses. Here we present datasets on these common and species-specific responses that complement the original study (Bruno et al. Computational and Structural Biology Journal). These data serve to facilitate further fundamental research on the immune response to opportunistic pathogenic fungi such as A. fumigatus, C. albicans, and R. oryzae.
| S-EPMC8039545 | biostudies-literature
Project description:Endozoicomonas coral host response
| PRJNA753662 | ENA
Project description:Sampangine, a plant-derived alkaloid found in the Annonaceae family, exhibits strong inhibitory activity against the opportunistic fungal pathogens Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. In the present study, transcriptional profiling experiments coupled with the analysis of mutants were performed in an effort to elucidate its mechanism of action. Using Saccharomyces cerevisiae as a model organism, we show that sampangine produces a transcriptional response indicative of hypoxia, altering the expression of genes known to respond to low oxygen conditions. Several additional lines of evidence obtained suggest that these responses could involve effects on heme. First, the hem1 deletion mutant lacking the first enzyme in the heme biosynthetic pathway showed increased sensitivity to sampangine, and exogenously supplied hemin partially rescued the inhibitory activity of sampangine in wild-type cells. In addition, heterozygous mutants with deletions in genes involved in five out of eight steps in the heme biosynthetic pathway showed increased susceptibility to sampangine. Furthermore, spectral analysis of pyridine extracts indicated significant accumulation of free porphyrins in sampangine-treated cells. Transcriptional profiling experiments were also performed in C. albicans to investigate the response of a pathogenic fungal species to sampangine. Taking into account the known differences in the physiological responses of C. albicans and S. cerevisiae to low oxygen, significant correlations were observed between the two transcription profiles suggestive of heme-related defects. Our results indicate that the antifungal activity of the plant alkaloid sampangine is due, at least in part, to perturbations in the biosynthesis or metabolism of heme. GSE10073: Gene expression response to the antifungal compound sampangine in S. cerevisiae GSE10075: Gene expression response to the antifungal compound sampangine in C. albicans Keywords: SuperSeries Refer to individual Series
2010-05-26 | E-GEOD-10104 | biostudies-arrayexpress