Project description:Our study provides considerable gene expression information of Trichophyton mentagrophytes at the transcriptional level, which will help accelerate the research on the antifungal medicine development. Additionally, we have demonstrated the feasibility of using the Illumina sequencing based DGE system for gene expression profiling, and have shed new light on functional studies of the genes involved in antifungal mechanisms of berberine hydrochloride and clotrimazole.
2019-03-20 | GSE80604 | GEO
Project description:Study on antifungal mechanism of quaternary ammonium salt
Project description:Dermatophytosis is a common and relevant zoonotic disease of public health concern, Various antifungal compounds, including clotrimazole, terbinafine, and ketoconazole have been reported for the treatment of dermatophytosis,In the present study,Transcriptome profile of T. mentagrophytes exposed to different drugs was performed in order to find the important drug antifungal active point.
Project description:A systematic approach allowing the identification of the molecular way-of-action of novel potential drugs represents the golden-tool for drug-discovery. While high-throughput screening technologies of large libraries is now well established, the assessment of the drug targets and mechanism of action is still under development. Taking advantage of the yeast model Saccharomyces cerevisiae, we herein applied BarSeq, a Next Generation Sequencing-based method to the analysis of both haploinsufficiency and homozygous fitness effects of a novel antifungal drug ('089') compared to the well-known antifungal ketoconazole. '089' was a novel compound identified in during a screen for antifungal drugs, as it was showing fungicidal effects, and able to affect the yeast fitness at the mitochondrial level (Stefanini et al., 2010. (Dissection of the Effects of Small Bicyclic Peptidomimetics on a Panel of Saccharomyces cerevisiae Mutants;.J Biol Chem, 285: 23477-23485.) Integrative bioinformatic analysis of BarSeq, whole genome expression analysis and classical biological assays identified the target and cell pathways affected by the novel antifungal. Confirmation of the effects observed in the yeast model and in pathogenic fungi further demonstrated the reliability of the multi-sided approach and the novelty of the targets and way-of-action of the new class of molecules studied representing a valuable source of novel antifungals.
Project description:Fusarium spp. are fungal pathogens of humans and plants. Fusarium oxysporum and Fusarium solani are important species isolated from infections such as onychomycosis, fungal keratitis, invasive infections, and disseminated diseases. These pathologies have a very difficult therapeutic management and poor therapeutic responses, especially in patients with disseminated infection. Little information is available regarding the molecular mechanisms responsible for antifungal resistance in these fungi. methods: In this study, we performed a quantitative analysis of the transcriptional profile of F. oxysporum and F. solani, challenged with amphotericin B (AMB) and posaconazole (PSC) using RNA-seq. Quantitative real-time reverse transcription PCR (qRT-PCR) was used to validate the results results: Several genes related to mechanisms of antifungal resistance such as efflux pumps, ergosterol pathway synthesis, and responses to oxidative stress were found. Genes such as ERG11, ERG5, the Major Facilitator Superfamily (MFS), thioredoxin, and different dehydrogenase genes may explain the reduced susceptibility of Fusarium spp. against azoles and the possible mechanisms that may play an important role in induced resistance against polyenes. conclusions: Important differences in the levels of transcriptional expression were found between F. oxysporum and F. solani exposed to the two different antifungal treatments. Knowledge on the gene expression profiles and gene regulatory networks in Fusarium spp. during exposure to antifungal compounds, may help to identify possible molecular targets for the development of novel, better, and more specific therapeutic compounds. profile transcriptional of Fusarium spp changed to antifungal treatments in vitro
Project description:In the current study, we set out to explore the developmental mechanism of antifungal resistance in this fungus using an in vitro experimental evolution strategy.
Project description:Fusarium spp. are fungal pathogens of humans and plants. Fusarium oxysporum and Fusarium solani are important species isolated from infections such as onychomycosis, fungal keratitis, invasive infections, and disseminated diseases. These pathologies have a very difficult therapeutic management and poor therapeutic responses, especially in patients with disseminated infection. Little information is available regarding the molecular mechanisms responsible for antifungal resistance in these fungi. methods: In this study, we performed a quantitative analysis of the transcriptional profile of F. oxysporum and F. solani, challenged with amphotericin B (AMB) and posaconazole (PSC) using RNA-seq. Quantitative real-time reverse transcription PCR (qRT-PCR) was used to validate the results results: Several genes related to mechanisms of antifungal resistance such as efflux pumps, ergosterol pathway synthesis, and responses to oxidative stress were found. Genes such as ERG11, ERG5, the Major Facilitator Superfamily (MFS), thioredoxin, and different dehydrogenase genes may explain the reduced susceptibility of Fusarium spp. against azoles and the possible mechanisms that may play an important role in induced resistance against polyenes. conclusions: Important differences in the levels of transcriptional expression were found between F. oxysporum and F. solani exposed to the two different antifungal treatments. Knowledge on the gene expression profiles and gene regulatory networks in Fusarium spp. during exposure to antifungal compounds, may help to identify possible molecular targets for the development of novel, better, and more specific therapeutic compounds.
Project description:The goals of this study are to compare C. glabrata transcriptome profiling (RNA-seq) upon exposure to the antifungal fluconazole in order to assess antifungal response. The role of the transcription factor Mar1 is clarified through comparison of the transcrptome profiles of WT and Mar1 mutant cells. mRNA profiles of WT and ∆mar1 were generated by deep sequencing, in duplicate, using Illumina HiSeq. The sequence reads that passed quality filters were analyzed with TopHat followed by HTSeq.
Project description:The goal of this study is to compare the C. glabrata transcriptome profile (RNA-seq) upon exposure to the antifungal fluconazole in either liquid or solid medium and assess differential antifungal response. The role of the coregulator PGD1 is clarified through comparison of the transcriptome profiles of WT and PGD1 mutant cells. mRNA profiles of WT and ∆pgd1 were generated by deep sequencing, in triplicate, using Illumina NextSeq. The sequence reads that passed quality filters were analyzed with TopHat followed by HTSeq.