Huangqin Decoction Exerts Antifungal Effects by Interfering with Energy Metabolism of Trichophyton rubrum with Glyoxylate Cycle as a Potential Target
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PROVIDER: PRJNA1282973 | ENA |
REPOSITORIES: ENA
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Project description:Background: The dermatophyte Trichophyton rubrum (T. rubrum) is a highly specialized filamentous fungus that infects keratinized tissues and is the most common pathogen isolated from human dermatophytosis. The clinical treatment of the infections is challenging due to the prolonged treatment duration, limited efficacy, antifungal resistance and adverse effects of available drugs. Huangqin decoction (HQD) is a classical traditional Chinese medicine (TCM) formula, whose inhibitory efficiency against T. rubrum was disclosed in our previous study. However, the responsible mechanisms are not well understood. Aim: This study aimed to elucidate the mode of action of Huangqin decoction (HQD) against T. rubrum as a whole by using transcriptome sequencing combined with verification of qRT-PCR and enzymatic activity assays. Methods: By treating T. rubrum with HQD at minimum inhibitory concentration (MIC), the differentially expressed genes (DEGs) of T. rubrum in response to HQD based on transcriptome profiles were recognized. Gene function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed functions and signaling pathways modulated by the DEGs. The transcriptome results were validated by quantitative real-time PCR (qRT-PCR). The potential targets were further explored using enzymatic activity assays. Results: At MIC, a total of 338 differentially expressed genes (DEGs) were detected in T. rubrum after HQD exposure compared with the control group (q-value < 0.05), of which 199 genes were significantly up-regulated and 139 genes were down-regulated. Gene function analysis indicated that COG functions of DEGs mainly covered “carbohydrate transport and metabolism” and “energy production and conversion”. The most frequently found GO terms were “metabolic process” and “catalytic activity”. KEGG enrichment analysis revealed that DEGs were predominately enriched in 6 pathways of “valine, leucine and isoleucine degradation”, “indole alkaloid biosynthesis”, “ABC transporters”, “synthesis and degradation of ketone bodies”, “starch and sucrose metabolism”, and “glyoxylate and dicarboxylate metabolism” (q-value < 0.05). Three KEGG pathways were closely related to energy metabolism, which was consistent with the COG and GO results. A subset of eight DEGs by the involvement of the biosynthesis and degradation of cell walls and energy metabolism including amino acid metabolism and the glyoxylate cycle were further confirmed by qRT-PCR and the results verified the transcriptome data. Enzymatic activity assays showed that compared to the control group, activities of citrate synthase (CS), aconitate hydratase (ACO) and isocitrate lyase (ICL) in the glyoxylate cycle were affected by HQD. Conclusion: The overall evidence suggested that the interference of energy metabolism might contribute to the mode of action of HQD against dermatophyte pathogen T. rubrum, and the glyoxylate cycle may be the potential antifungal target of HQD against the fungi. Our study provides a theoretical basis for the mechanisms of HQD upon T. rubrum infections and offers an important insight regarding the glyoxylate cycle especially enzyme isocitrate lyase as indispensable targets of the herbal formulations.
2025-06-28 | GSE300994 | GEO
Project description:Trichophyton mentagrophytes (T. mentagrophytes) is a prevalent pathogen that causes human and animal dermatophytosis. The clinical treatment of these infections is challenging due to the prolonged treatment duration, limited efficacy, antifungal resistance and side effects of existing drugs. It has been reported that the classic Traditional Chinese medicine (TCM) prescription Huangqin decoction (HQD) along with its principal ingredients could exhibit antifungal properties. Given the valued advantages of TCM such as broad-spectrum antifungal activity, low incidence of drug resistance and low toxicity, this study investigated the antifungal activity of HQD against T. mentagrophytes and explored the potential inhibitory mechanism, aimed to provide new clues for the treatment of dermatophytosis. By detecting minimal inhibitory concentration (MIC) using the broth microdilution method, the result showed that HQD could significantly inhibit the growth of T. mentagrophytes, with a MIC of 3.13 mg/mL. The transcriptome sequencing and quantitative real-time PCR (qRT-PCR) technology were combined to shed light on the complicated adaptive responses of T. mentagrophytes upon HQD. The results demonstrated that a total of 730 differentially expressed genes (DEGs) were detected in T. mentagrophytes after HQD exposure, of which 547 were up-regulated and 183 were down-regulated. These DEGs were abundant in “single-organism metabolic process”, “catalytic activity” and “oxidoreductase activity”, and were significantly enriched in seven signaling pathways including glutathione metabolism, DNA replication, glyoxylate and dicarboxylate metabolism, taurine and hypotaurine metabolism, carotenoid biosynthesis, ubiquitin mediated proteolysis, and cyanoamino acid metabolism. The results of transcriptome profiling were verified using qRT-PCR for a subset of 10 DEGs. The overall evidence indicated that HQD had a significant anti-dermatophyte activity through the modulation of glutathione metabolism by regulating GST, γ-GT genes, the inhibition of DNA replication pathway by downgrading MCM3, MCM5, RNaseH1 genes, and the repressed expression of PSD gene related to phospholipid synthesis in T. mentagrophytes.
2025-01-29 | GSE287990 | GEO
Project description:A cDNA microarray was constructed from the expressed sequence tags (ESTs) of different developmental stages, and transcriptional profiles of the responses to 5-Flucytosine were determined. Keywords: Expression profiling by array The expression profiles of Trichophyton rubrum treated with 5-Flucytosine were compared to those of Trichophyton rubrum without drug. Each treatment has three replicates.
2010-05-19 | E-GEOD-12861 | biostudies-arrayexpress
Project description:A cDNA microarray was constructed from the expressed sequence tags (ESTs) of different developmental stages, and comparative genome hybridization based on microarray procedures were carried out. Dermatophyte species are classified into three genera: Epidermophyton, Microsporum, and Trichophyton. To determine the relationship between these three groups comparative genome hybridization were used in our experiment. Trichophyton rubrum genmic DNA was reference DNA and labelled by Cy3 while the other dermatophytes genomic DNA were test DNA and labelled by CY5. Test and reference DNA were co-hybridized with the T. rubrum cDNA microarray and the numbers of genes shared between each species and T. rubrum were determined. Keywords: Comparative Genomic Hybridization We used a Trichophyton rubrum cDNA microarray prepared in our lab through comparative genome hybridization of genomic DNA of 21 dermatophyte strains (belonging to 20 species) to elucidate the taxonomy and evolution profiles of 20 dermatophyte species. The numbers of genes shared between each species and T. rubrum were determined. Each strain DNA hybridized for 3 times. The slides were separated into three groups base on different datasets.
2010-05-03 | E-GEOD-7909 | biostudies-arrayexpress
Project description:A cDNA microarray was constructed from the expressed sequence tags (ESTs) of different developmental stages, and comparative genome hybridization based on microarray procedures were carried out. Dermatophyte species are classified into three genera: Epidermophyton, Microsporum, and Trichophyton. To determine the relationship between these three groups comparative genome hybridization were used in our experiment. Trichophyton rubrum genmic DNA was reference DNA and labelled by Cy3 while the other dermatophytes genomic DNA were test DNA and labelled by CY5. Test and reference DNA were co-hybridized with the T. rubrum cDNA microarray and the numbers of genes shared between each species and T. rubrum were determined. Keywords: Comparative Genomic Hybridization
2010-05-04 | GSE7909 | GEO
Project description:Conidia are considered to be the primary cause of skin and nail infections by Trichophyton rubrum. A cDNA microarray containing 10112 ESTs was developed and used to estimate the relative gene expression levels and changes of gene expression during conidial germination in time-course experiments. Keywords: time course
2007-03-27 | GSE5083 | GEO
Project description:Trichophyton rubrum, an anthropophilic and cosmopolitan fungus, is the most common agent of superficial mycoses, causing rarely deep dermatophytosis in immunocompromised hosts.
2011-10-03 | GSE15532 | GEO
Project description:Antifungal activity and potential inhibitory mechanism of Huangqin decoction on Trichophyton mentagrophytes
| PRJNA1215414 | ENA
Project description:Trichophyton rubrum, an anthropophilic and cosmopolitan fungus, is the most common agent of superficial mycoses, causing rarely deep dermatophytosis in immunocompromised hosts. In this study, an infection condition of T. rubrum was modeled by adding human skin sections into a limited medium containing glucose to monitor T. rubrum gene expression patterns using cDNA microarrays on a global level. We found that exposure to human skin resulted in up-regulation of the expression levels of T. rubrum genes related to many cellular and biological processes, including transcription and translation, metabolism and secondary transport, stress response, and signaling pathways. These results provide a reference set of T. rubrum genes whose expression patterns change upon infection and reveal previously unknown genes that probably corresponding to proteins that should be considered as virulence factor candidates and potential new drug targets for T. rubrum infections.
2011-10-02 | E-GEOD-15532 | biostudies-arrayexpress