Transcriptome profile of T. mentagrophytes exposed to different drugs
Ontology highlight
ABSTRACT:
ORGANISM(S): Trichophyton mentagrophytes
PROVIDER: GSE162331 | GEO | 2021/04/13
REPOSITORIES: GEO
Similar Datasets
Project description:A systematic approach allowing the identification of the molecular way of action of novel potential drugs still represents the golden-tool for drug-discovery researchers. 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 compared to the well-known antifungal, ketoconazole. 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 as well as in pathogenic fungi further demonstrated the reliability of the multi-sided approach and the novelty of the targets and mode of action of the new class of molecules studied that thus represent a valuable source of novel antifungals.
2016-12-30 | GSE42418 | GEO
Project description:The systemic infections by peptogenous fungi member of the genera Candida and Aspergillus represent a serious threat for public health. During previous research we have successfully identified a family of compounds active against different Candida spp. including strains resistant to antifungal drugs currently on the market. We have further refined our knowledge on this field by identifying a possible molecular target that could justify the activity of these compounds. The research of the mode of action of the compounds object of this manuscript was supported also by fluorescent microscopy of labeled derivatives. Transcriptional data indicates that one of the macrocyclic antifungal induces a drug response involving ATP binding cassette transporters. Moreover the data show that the macrocyclic antifungal decrease expression of cell wall biosynthesis genes. Moreover, the quality of the compounds and their potential was tested in vivo revealing a promising profile in particular against fungal infection caused by resistant strains
2015-04-01 | GSE65396 | GEO
Project description:The systemic infections by peptogenous fungi member of the genera Candida and Aspergillus represent a serious threat for public health. During previous research we have successfully identified a family of compounds active against different Candida spp. including strains resistant to antifungal drugs currently on the market. We have further refined our knowledge on this field by identifying a possible molecular target that could justify the activity of these compounds. The research of the mode of action of the compounds object of this manuscript was supported also by fluorescent microscopy of labeled derivatives. Transcriptional data indicates that one of the macrocyclic antifungal induces a drug response involving ATP binding cassette transporters. Moreover the data show that the macrocyclic antifungal decrease expression of cell wall biosynthesis genes. Moreover, the quality of the compounds and their potential was tested in vivo revealing a promising profile in particular against fungal infection caused by resistant strains Gene expression was measured in Candida albians CAF2-1 exposed to the macrocyclic compound FR59 at 3 µM at two time points (15 min and 45 min), The one-color system was used. Three independent experiments were performed using non-exposed cells, 15 min and 45 min exposed cells.
2015-04-01 | E-GEOD-65396 | biostudies-arrayexpress
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.
2016-04-30 | E-SYBR-6 | biostudies-arrayexpress
Project description:Fungal infections have become a clinical challenge due to the emergence of drug-resistance of invasive fungi and a rapid increase of novel pathogens. The development of drug resistance has further restricted the use of antifungal agents. Therefore, there is anurgentneedto searchforalternativetreatmentoptions for Cryptococcus neoformans (C. neoformans). Disulfiram (DSF) has a high human safety profile and promising applications as an antiviral, antifungal, antiparasitic, and anticancer agent. In contrast, the effect of DSF on Cryptococcus has yet to be thoroughly researched. This study investigated the antifungal effect and mechanism of DSF againstC. neoformansto provide a new theoretical foundation for treating Cryptococcal infections. In vitro studies demonstrated that DSF inhibitedCryptococcusat minimum inhibitory concentrations (MICs) ranging from 1.0 to 8.0 μg/mL. Combined antifungal effects were also observed with 5-fluorocytosine, amphotericin B, terbinafine, or ketoconazole. In vivo, DSF exerted asignificantprotectiveeffectforGalleria mellonella infected with C. neoformans.Mechanistic investigations showed that DSF dose-dependently inhibited the melanin, urease, acetaldehyde dehydrogenase, capsule, and biofilm formation or viability ofC. neoformans.Further study indicated DSF affectedC. neoformansby interfering with multiple biological pathways, including replication, metabolism, membrane transport, and biological enzyme activity. Potentially essential targets of these pathways included acetaldehyde dehydrogenase, catalase, ATP-binding cassette transporter (ABC transporter) AFR2, and iron-sulfur cluster transporter ATM1. These findings contribute to the understanding of mechanisms inC. neoformans, and provide new insights for the application of DSF.
2023-12-31 | GSE248987 | GEO
Project description:New antifungal drugs are urgently needed due to the currently limited selection, the emergence of drug resistance, and the toxicity of several commonly used drugs. To identify drug leads, we screened small molecules using a Saccharomyces reporter bioassay in which the yeast heterologously expresses Hik1, a group III hybrid histidine kinase (HHK) from Magnaporthe grisea. Group III HHKs are integral in fungal cell physiology, and highly conserved throughout this kingdom; they are absent in mammals, making them an attractive drug target. Our screen identified compounds 13 and 33, which showed robust activity against numerous fungal genera including Candida, Cryptococcus and molds such as Aspergillus and Rhizopus. Drug-resistant Candida from patients were also highly susceptible to compounds 13 and 33. While the compounds do not act directly on HHKs, microarray analysis showed that compound 13 induced transcripts associated with oxidative stress, and compound 33, transcripts linked with heavy metal stress. Both compounds were highly active against Candida biofilm, in vitro and in vivo, and exerted synergy with fluconazole, which was inactive alone. Thus, we identified potent, broad-spectrum antifungal drug leads from a small molecule screen using a high-throughput, yeast reporter bioassay. Two-color experimental design testing the effects of 2 antifungal compounds (13 and 33) after 0, 20, 40 60 min. In the referred publication, the t=20, 40, 60 data was normalized against the t=0 data
2012-04-30 | E-GEOD-35105 | biostudies-arrayexpress
Project description:One antifungal agent, terbinafine(TRB), has specific activity against dermatophytes.A cDNA microarray was constructed from the expressed sequence tags (ESTs) of different developmental stages, and transcriptional profiles of the responses to TRB were determined. Some class-specific and mechanism-independent changes in gene expression were found. Keywords: original article
2008-02-04 | GSE6951 | GEO
Project description:Hantavirus infection causing zoonotic diseases with a high mortality rate in humans has long been a global public health concern. Over the past decades, accumulating evidences suggest that long noncoding RNAs (lncRNAs) play key regulatory roles in innate immunity. However, the involvement of host lncRNAs in hantaviral control remains uncharacterized. To explore the potential role of long non-coding RNAs in host innate immune responses, DGE analysis of HUVECs for whole genome profiling was performed at 24 hours post HTNV infection.
2016-11-17 | GSE89950 | GEO
Project description:HT1080 fibrosarcoma cells were treated with cytostatic drugs and analysed on Affymetrix microarray to identify genes and pathways regulated by these compounds. The array images were processed using Affymetrix MAS 5.0 software. and normalized by global scaling or scaled to a polyA+ spike mask Keywords = Cytostatic drugs Keywords = Actinomycin D Keywords = Doxorubicin Keywords = Vincristine Keywords = apoptosis Keywords: ordered
2006-02-04 | GSE2238 | GEO
Project description:Campylobacter jejuni is a major zoonotic pathogen transmitted to humans via the food chain. C. jejuni is prevalent in chickens, a natural reservoir for this pathogenic organism. Due to the importance of macrolide antibiotics in clinical therapy of human campylobacteriosis, development of macrolide resistance in Campylobacter has become a concern for public health.To facilitate understanding the molecular basis associated with the fitness difference between Erys and Eryr Campylobacter, we compared the transcriptomes between ATCC 700819 and its isogenic Eryr transformant T.L.101 using DNA microarray.
2011-11-02 | GSE33330 | GEO