Transcriptome analysis uncovers PacC-mediated metabolic adaptation in the dermatophyte pathogen Tricophyton interdigitale
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ABSTRACT:
ORGANISM(S): Trichophyton interdigitale
PROVIDER: GSE313401 | GEO | 2026/04/01
REPOSITORIES: GEO
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Project description:Transcriptome analysis uncovers PacC-mediated metabolic adaptation in the dermatophyte pathogen Tricophyton interdigitale
| PRJNA1379443 | ENA
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 Three independently prepared T. rubrum 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. Pairwise transcriptional comparisons, i.e. soy versus Sabouraud, keratin-soy versus Sabouraud and keratin-soy versus soy were done. The total number of slides in this study was 9.
2008-12-30 | E-GEOD-11711 | biostudies-arrayexpress
Project description:Purpose: We evaluated T. rubrum transcriptome using high-throughput RNA-sequencing (RNA-seq) technology aiming to identify metabolic pathways modulated the development in keratin. Methods: T. rubrum strain CBS118892 was inoculated into 100 mL Sabouraud dextrose broth, and incubated under agitation at 28 °C for 96 h. Mycelia were aseptically transferred into 100 mL minimal medium (MM) at pH 5.0 containing 70 mM nitrate and 50 mM glucose (control) or 0.5% (w/v) bovine keratin (treatment) as the carbon source. The cultures were incubated under agitation at 28 °C for 24 h, 48 h, or 96 h. Equal amounts of RNA from three independent biological replicates of keratin or glucose cultures were sequenced with a Hiseq 2000 sequencer. Paired-end reads 150 bp in size were generated. Raw read data obtained were filtered for quality control by FastQC tool and trimmed with Trimmomatic to remove adapters and Illumina-specific sequences. Trimmed paired-end reads from each sample were aligned to the T. rubrum reference genome. Gene-level read counts were quantified with STAR’s ‘-quantModeGeneCounts’ parameter. Differential expression was analyzed with the DESeq2 bioconductor package. A Benjamini-Hochberg correction adjusted the P threshold and was applied to reveal statistically significant changes in gene expression levels. It was set to 0.05, with a log2 fold change ± 1.5 and postulated as a significantly modulated transcript abundance level. Genes surpassing these thresholds are hereinafter referred to as differentially expressed genes (DEG). They were functionally categorized with the Gene Ontology (GO) terms assigned by the Blast2GO algorithm. Highly represented categories were determined by enrichment analysis with the BayGO algorithm. Results: Our results present adaptive strategies in response to culture media. The global modulation in response to keratin supports fungal virulence and proper adaptation to the environment, in comparison to the availability of glucose as a carbon source. Conclusions: Our results revealed a profile of the adaptive events to the host environment, crucial to the establishment and maintenance of the infection. The observed metabolic modulation is necessary for fungus survival and perpetuation in the initial steps of the infective process in their host.
2019-09-19 | GSE134406 | GEO
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: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: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:Purpose: We aimed to gain more aspects about Stua-regulated processes in T. rubrum by assessing the global gene expression after its growth on keratin or glucose sources. Methods: T. rubrum strain CBS118892 and the null mutant strain ΔstuA were inoculated into 100 mL Sabouraud dextrose broth, and incubated under agitation at 28 °C for 96 h. Mycelia were aseptically transferred into 100 mL minimal medium (MM) at pH 5.0 containing 70 mM nitrate and 50 mM glucose (control) or 0.5% (w/v) bovine keratin (test condition) as an alternative carbon source. The cultures were incubated under agitation at 28 °C for 24 h, 48 h, or 96 h. Equal amounts of RNA from three independent biological replicates of keratin or glucose cultures were sequenced with a NextSeq 500 sequencer. Paired-end reads of 150 bp in size were generated. Raw data obtained were processed for quality control by FastQC tool and trimmed with Trimmomatic to remove adapters and Illumina-specific sequences. Trimmed paired-end reads from each sample were aligned to the T. rubrum reference genome. Gene-level read counts were quantified with STAR’s ‘-quantModeGeneCounts’ parameter. Differential expression was analyzed with the DESeq2 bioconductor package. A Benjamini-Hochberg correction adjusted the P threshold and was applied to reveal statistically significant changes in gene expression levels. It was set to 0.05, and a cut off threshold of ±1.5 log2-fold change was set to reveal statistically significant changes in expression levels, and referred as differentially expressed genes (DEG). DEGs were functionally categorized with the Gene Ontology (GO) terms assigned by the Blast2GO algorithm. Ultimately, the most representative categories for each experimental condition were identified by enrichment analysis using the BayGO algorithm . Results: Our data showed the involvement of Stua in biological processes related to carbon central metabolism and glycerol catabolism, ROS metabolism, and cell wall construction. The deep changes in carbohydrate metabolism might be responsible for significant alteration in cell wall pattern and consequently in cell to cell interaction and adhesion as we also demonstrated in this study. The mutant strain presented an impairment in biofilm production and promoted an increase in pro-inflammatory cytokine secretion. Moreover, we displayed a StuA-dependent regulation on catalase genes. Conclusions: In conclusion, our data demonstrated the multitude of regulatory targets in TrStuA with a critical role in central metabolism that ultimately may be responsible to trigger a cascade of secondary effects with strong impacts on fungal physiology and virulence traits.
2021-05-14 | GSE163357 | 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
2010-03-05 | GSE15873 | GEO
Project description:Alkaline pH triggers an adaptation mechanism in fungi that is mediated by Rim101/PacCp, a zinc finger transcription factor. To identify the genes under its control in Ustilago maydis, we performed microarray analyses, comparing gene expression in a wild type strain vs a rim101/pacC mutant of the fungus. In this study we obtained evidence of the large number of genes regulated mostly directly, but also indirectly (probably through regulation of other transcription factors) by Rim101/PacCp, including proteins involved in a large number of physiological activities of the fungus. Our analyses suggest that the response to alkaline conditions under the control of the Pal/Rim pathway involves changes in the cell wall and plasma membrane through alterations in their lipid, protein, and polysaccharide composition, changes in cell polarity, actin cytoskeleton organization, and budding patterns. Also as expected, adaptation involves regulation by Rim101/PacC of genes involved in the meiotic functions, such as recombination and segregation, and expression of genes involved in ion and nutrient transport, as well as general vacuole functions. The mutant analyzed in this study is described in PMID 15947192
2014-07-21 | GSE53341 | GEO
Project description:Colletotrichum gloeosporioides, a widely distributed economically important agent in postharvest fruit disease thrives by massive secretion of ammonia to alkalize its environment and activate its pathogenicity genes. We sequenced the C. gloeosporioides transcriptomes of WT and a ∆pacC mutant, a major gene regulator under changing pH, under pH 7.0 in order to examine pacC regulation. Transcriptome analysis of the ∆pacC strain showed that 468 and 458 genes were up or down regulated, respectively. Both the up and down regulated genes were clustered into similar functions including: transporters to maintain cellular homeostasis, cell wall degrading enzymes to optimize pathogenicity and GATA-like transcription factors. Suggesting that activation of pacC under alkaline condition regulates genes expression to fit their optimal PKa. The transcript level predictions were verified by growth in different pH and fruit infection. Further analyses showed pacC binding sites were over-represented in the promoters of the pacC up-regulated genes but not in the promoters of the down-regulated genes, where instead, GATA-like binding sites were prominent. Evolutionary conservation of pacC control was sought by examining the gene orthologs in 5 fungal genomes whose members display contrasting alkaline or acidifying pathogenicity strategies. The results showed that irrespective of pathogen colonization strategy, only orthologs of up-regulated genes showed over-representation of pacC binding sites. Significantly, the down regulated orthologs revealed cross-genome over-representation of GATA transcription factor binding sites. Thus, pacC is a phylogenetically conserved fungal mechanism exerting dual pH control for maintaining homeostasis and pathogenicity in changing environments.
2013-11-21 | GSE41844 | GEO