Challenges posed to the dermatophyte Trichophyton rubrum by sertraline a drug predominantly used to treat human depression
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA904223 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22372900_1.fastq.gz | Fastqsanger.gz | |||
| SRR22372900_2.fastq.gz | Fastqsanger.gz | |||
| SRR22372901_1.fastq.gz | Fastqsanger.gz | |||
| SRR22372901_2.fastq.gz | Fastqsanger.gz | |||
| SRR22372902_1.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: We evaluated T. rubrum transcriptome using high-throughput RNA-sequencing (RNA-seq) technology aiming to identify metabolic pathways modulated by the antidepressive sertraline. Methods: We employed the next-generation sequencing (RNA-seq) approach to identify the central responsively genes related to SRT effects. Results: we identified the main effects of sertraline as the disturbance of maintaining the fungal cell wall and plasmatic membrane stability targeting ergosterol biosynthesis. SRT also modulated genes encoding enzymes related to fungal energy metabolism, cellular detoxification, and defense against oxidative stress Conclusions: Our findings provide insights into a specific molecular network interaction operative for main-taining metabolic stability perturbed by SRT drug showing relevant targets for its strategic use in the dermatophytosis field.
2023-02-23 | GSE218521 | GEO
Project description:RNA seq data of Hep3B-control, Hep3B-sertraline, Hep3B-XL413, Hep3B-XL413-sertraline, Huh7-control, Huh7-sertraline, Huh7-XL413, Huh7-XL413-sertraline cells
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Project description:Hep3B and Huh7 cells pre-treated with XL413 for 10 days to induce senescence prior to sertraline treatment for 24 hours. For RNA sequencing, the library was prepared using TruSeq RNA sample prep kit according to the manufacturer’s protocol (Illumina). Gene set enrichment analysis was performed using gene set enrichment analysis software.
2018-10-16 | GSE121277 | GEO
Project description:Pharmaceutical chemicals used in human medicine are released into surface waters via municipal effluents and pose a risk for aquatic organisms. Among these substances are selective serotonin reuptake inhibitors (SSRIs) which can affect aquatic organisms at sub ppb concentrations. To better understand biochemical pathways influenced by SSRIs, evaluate changes in the transcriptome, and identify gene transcripts with potential for biomarkers of exposure to SSRIs; larval zebrafish Danio rerio were exposed (96 h) to two concentrations (25 and 250 µg/L) of the SSRIs, fluoxetine and sertraline, and changes in global gene expression were evaluated (Affymetrix GeneChip® Zebrafish Array). Significant changes in gene expression (>=1.7 fold change, p<0.05) were determined with Partek® Genomics Suite Gene Expression Data Analysis System and ontology analysis was conducted using Molecular Annotation System 3. The number of genes differentially expressed after fluoxetine exposure was 288 at 25 µg/L and 131 at 250 µg/L; and after sertraline exposure was 33 at 25 µg/L and 52 at 250 µg/L. Five genes were differentially regulated in all treatments relative to control, suggesting that both SSRIs share some similar molecular pathways. Among them, expression of the gene coding for FK506 binding protein 5 (FKBP5), which is annotated to stress response regulation, was highly down-regulated in all treatments (results confirmed by qRT-PCR). Gene ontology analysis indicated that regulation of stress response and cholinesterase activity were critical functions influenced by these SSRIs, and suggested that changes in the transcription of FKBP5 or acetylcholinesterase could be useful biomarkers of SSRIs exposure in wild fish. Zebrafish (Danio rerio) were obtained from the Zebrafish Research Facility maintained at the Center for Environmental Biotechnology at the University of Tennessee. Fish husbandry, spawning, and experimental procedures were conducted with approval from the UT Insititutional Animal Care and Use Committee (Protocol #1690-1007). Water for holding fish and conducting experiments (hereafter referred to as fish water) consisted of MilliQ water (Millipore, Bedford, MA) with ions added: 19 mg/L NaHCO3, 1 mg/L sea salt (Instant Ocean Synthetic Sea Salt, Mentor, OH), 10 mg/L CaSO4, 10 mg/L MgSO4, 2 mg/L KCl. Embroyos were obtained by spawning adult fish with no history of contaminant exposure. Fertilization of embryos took place at the same time (<15 minutes), such that larvae used in experiments were of similar age at the time of exposure. All activities (maintenance of adult fish, spawning, and experiments) were conducted in an environmental chamber with a temperature of 27 +/- 1 C and 14:10h light:dark photoperiod. Larval zebrafish (72 hpf) were exposed for 96 h in 200ml fish water containing appropirate amount of SSRI stock (i.e. fluoxetine or sertraline). There were four SSRIs treatments (25 and 250 ug/L fluoxetine and 25 and 250 ug/L sertraline) and one control (no SSRIs) with triplicate beakers and each beaker contained about 100 larval fish. During exposure for 96 hours, beakers were kept covered to prevent water evaporation and fish were not fed (i.e., fish consumed their yolk sac).
2012-09-06 | E-GEOD-31712 | biostudies-arrayexpress
Project description:Enhancers predominantly control transcription initiation
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Project description:Although dermatophytes are the most common agents of superficial mycoses in humans and animals, the molecular basis of the pathogenicity of these fungi is largely unknown. In vitro digestion of keratin by dermatophytes is associated with the secretion of multiple proteases, which are assumed to be responsible for their particular specialization to colonize and degrade keratinized host structures during infection. To address this hypothesis a guinea pig infection model was established for the zoophilic dermatophyte Arthroderma benhamiae which causes highly inflammatory cutaneous infections in humans and rodents. Microarray analysis revealed a distinct in vivo protease gene expression profile in the fungal cells, which is surprisingly different from the pattern elicited during in vitro growth on keratin. Instead of the major in vitro expressed proteases others were activated specifically during infection. These enzymes are therefore suggested to fulfill important functions that are not exclusively associated with the degradation of keratin. As the most upregulated in vivo specific A. benhamiae sequence we discovered the gene encoding the serine protease subtilisin 6, which is a known major allergen in the related dermatophyte Trichophyton rubrum and putatively linked to host inflammation. In addition, our approach identified other candidate pathogenicity related factors in A. benhamiae, such as genes encoding key enzymes of the glyoxylate cycle and an opsin-related protein. This first broad transcriptional profiling approach during dermatophyte infection gives new molecular insights into pathogenicity associated mechanisms that make these microorganisms the most successful etiologic agents of superficial mycoses. Keywords: Two-condition experiment, strong proteolytic activity in the supernatant versus no proteolytic activity or infected tissue versus no proteolytic activity
2010-03-05 | GSE15873 | GEO
Project description:Pharmaceutical chemicals used in human medicine are released into surface waters via municipal effluents and pose a risk for aquatic organisms. Among these substances are selective serotonin reuptake inhibitors (SSRIs) which can affect aquatic organisms at sub ppb concentrations. To better understand biochemical pathways influenced by SSRIs, evaluate changes in the transcriptome, and identify gene transcripts with potential for biomarkers of exposure to SSRIs; larval zebrafish Danio rerio were exposed (96 h) to two concentrations (25 and 250 µg/L) of the SSRIs, fluoxetine and sertraline, and changes in global gene expression were evaluated (Affymetrix GeneChip® Zebrafish Array). Significant changes in gene expression (>=1.7 fold change, p<0.05) were determined with Partek® Genomics Suite Gene Expression Data Analysis System and ontology analysis was conducted using Molecular Annotation System 3. The number of genes differentially expressed after fluoxetine exposure was 288 at 25 µg/L and 131 at 250 µg/L; and after sertraline exposure was 33 at 25 µg/L and 52 at 250 µg/L. Five genes were differentially regulated in all treatments relative to control, suggesting that both SSRIs share some similar molecular pathways. Among them, expression of the gene coding for FK506 binding protein 5 (FKBP5), which is annotated to stress response regulation, was highly down-regulated in all treatments (results confirmed by qRT-PCR). Gene ontology analysis indicated that regulation of stress response and cholinesterase activity were critical functions influenced by these SSRIs, and suggested that changes in the transcription of FKBP5 or acetylcholinesterase could be useful biomarkers of SSRIs exposure in wild fish.
2012-09-06 | GSE31712 | GEO
Project description:Although dermatophytes are the most common agents of superficial mycoses in humans and animals, the molecular basis of the pathogenicity of these fungi is largely unknown. In vitro digestion of keratin by dermatophytes is associated with the secretion of multiple proteases, which are assumed to be responsible for their particular specialization to colonize and degrade keratinized host structures during infection. To address this hypothesis a guinea pig infection model was established for the zoophilic dermatophyte Arthroderma benhamiae which causes highly inflammatory cutaneous infections in humans and rodents. Microarray analysis revealed a distinct in vivo protease gene expression profile in the fungal cells, which is surprisingly different from the pattern elicited during in vitro growth on keratin. Instead of the major in vitro expressed proteases others were activated specifically during infection. These enzymes are therefore suggested to fulfill important functions that are not exclusively associated with the degradation of keratin. As the most upregulated in vivo specific A. benhamiae sequence we discovered the gene encoding the serine protease subtilisin 6, which is a known major allergen in the related dermatophyte Trichophyton rubrum and putatively linked to host inflammation. In addition, our approach identified other candidate pathogenicity related factors in A. benhamiae, such as genes encoding key enzymes of the glyoxylate cycle and an opsin-related protein. This first broad transcriptional profiling approach during dermatophyte infection gives new molecular insights into pathogenicity associated mechanisms that make these microorganisms the most successful etiologic agents of superficial mycoses. Keywords: Two-condition experiment, strong proteolytic activity in the supernatant versus no proteolytic activity or infected tissue versus no proteolytic activity Three independently prepared A. benhamiae replicates grown in each of the three media, Sabouraud, soy and keratin-soy medium (designated SabA/B/C, soyA/B/C and keratin-soyA/B/C) were used. ARN from skin samples and fungus together of Guinea Pig infected with A. benhamieae were prepared. Pairwise transcriptional comparisons, i.e. soy versus Sabouraud, keratin-soy versus Sabouraud and Guinea Pig infected versus Sabouraud were done. The total number of slides in this study was 18.
2010-03-04 | E-GEOD-15873 | biostudies-arrayexpress
Project description:Dermatophytes are highly specialized filamentous fungi which cause the majority of superficial mycoses in humans and animals. The high secreted proteolytic activity of these microorganisms during growth on proteins is assumed to be linked with their particular ability to exclusively infect keratinized host structures such as skin stratum corneum, hair and nails. Individual secreted dermatophyte proteases were recently described and linked with the in vitro digestion of keratin. However, the overall adaptation and transcriptional response of dermatophytes during protein degradation is largely unknown. To address this question, we constructed a cDNA microarray for the human pathogenic dermatophyte Trichophyton rubrum, which is based on transcripts of the fungus grown on proteins. Gene expression profiling during growth of T. rubrum on soy and keratin displayed the activation of a large set of genes encoding endo- and exoproteases. In addition, other specifically induced factors with potential implication in protein utilization were identified, including heat shock proteins, transporters, metabolic enzymes, transcription factors and hypothetical proteins with unknown function. This broad-scale transcriptional analysis of dermatophytes during growth on proteins reveals new putative pathogenicity related host adaptation mechanism of these human pathogenic fungi. Keywords: Two-condition experiment, strong proteolytic activity in the supernatant versus no proteolytic activity
2008-12-31 | GSE11711 | GEO
Project description:Selective serotonin reuptake inhibitors (SSRIs) are one of the most prescribed antidepressant classes in recent decades, with the development of numerous variants. While the primary action of these medications involves the inhibition of serotonin reuptake, the observed therapeutic efficacy exhibits interindividual variability. In order to elucidate the molecular mechanisms underlying their pharmacological actions, this study examined the alteration in the transcriptome following treatment of each SSRI—fluoxetine, sertraline, or citalopram— or vehicle in cultured cortical neurons and the medial prefrontal cortex (mPFC) of mice (Mus musculus, Slc:ICR).
2025-03-30 | GSE292948 | GEO