Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1161802 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30681804_1.fastq.gz | Fastqsanger.gz | |||
| SRR30681805_1.fastq.gz | Fastqsanger.gz |
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Project description:Aspergillus terreus is an emerging fungal pathogen in immunocompromised patients. Due to intrinsic resistance of AmB against A. terreus and acquiring resistance to azoles, alternative antifungal strategy needs investigation. Thus, we explored the activity of phytochemicals such as Shikonin, gallic acid, coumaric acid and quercetin against A. terreus. Amongst these, shikonin showed significant inhibition at MIC50;2 µg/ml, considered for proteome profiling.
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Project description:RNA-seq data of the Amphotericin (AmB)-resistant Aspergillus strain 211 and its AmB-susceptible sectorized derivative with and without AmB treatment
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Project description:The filamentous fungus Aspergillus fumigatus is an opportunistic human pathogen, which can cause mycoses and allergies in susceptible individuals. With regard to therapy, the polyene drug amphotericin B (AmB) is still frequently used to treat Aspergillus fumigatus infections due to the fact that it remains effective against azole-resistant Aspergillus strains. AmB binds to ergosterol in the fungal membrane, but its mode of action and the fungal resistance mechanisms involved have not been completely elucidated yet. To get further insights into the drug mechanisms of AmB, we investigated the proteomic profile of A. fumigatus in response to AmB and its liposomal formulation by LC-MS/MS analysis. A significant increase (≥ 2-fold) in abundance of 202 different proteins in response to AmB and 193 in case of liposomal AmB was observed, while the level of 70 and 83 proteins decreased, respectively. In particular, the level of proteins anchored to the membrane, involved in catabolic processes, aromatic acid degradation, or secondary metabolism increased prominently. Of particular note was the more than 300-fold increase of a RTA1 domain-containing protein after AmB treatment. Fungal RTA-like proteins represent lipid-translocating exporters, which are characterized by multiple transmembrane regions and often confer resistance to toxic chemicals. Indeed, the deletion of the corresponding gene in A. fumigatus led to an increased susceptibility to AmB and other antifungal polyenes such as nystatin. Particularly worthy of mention is that some of the most significantly increased proteins included enzymes involved in the biosynthesis of secondary metabolites such as the prenylated polyphenol fumicycline as well as xanthocillin and hexadehydro-astechrome, which both form complexes with transition metals.
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Project description:Amphotericin B (AMB) is the most widely used polyene antifungal drug for the treatment of systemic fungal infections including invasive aspergillosis. We aimed to understand molecular targets of AMB in Aspergillus fumigatus (Afu) by genomic approaches. Amphotericin B (AMB) is the most widely used polyene antifungal drug for the treatment of systemic fungal infections including invasive aspergillosis. We aimed to understand molecular targets of AMB in Aspergillus fumigatus (Afu) by microarray and proteomic methods. Keywords: Aspergillus fumigatus treated with amphotericin B for 24 hours Experiment was performed in dye swap manner from two different biological replicates
2010-05-26 | E-GEOD-10505 | biostudies-arrayexpress
Project description:Amphotericin B (AMB) is the most widely used polyene antifungal drug for the treatment of systemic fungal infections including invasive aspergillosis. We aimed to understand molecular targets of AMB in Aspergillus fumigatus (Afu) by genomic approaches. Keywords: Aspergillus fumigatus treated with amphotericin B for 24 hours
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Project description:To identify peanut Aspergillus-interactive and Aspergillus-resistance genes, we carried out a large scale peanut Expressed Sequence Tag (EST) project followed by a peanut microarray study. For expression profiling, resistant and susceptible peanut cultivars were infected with a mixture of Aspergillus flavus and parasiticus spores. Microarray analysis identified 65 and 1 genes in resistant (C20) and susceptible (TF) cultivars, respectively, that were up-regulated in response to Aspergillus infection. In addition we identified 40 putative Aspergillus-resistance genes that were constitutively up-expressed in the resistant cultivar in comparison to the susceptible cultivar. Some of these genes were homologous to peanut, corn, and soybean genes previously shown to confer resistance to fungal infection. These results provide a comprehensive genome-scale platform for future studies focused on developing Aspergillus-resistant peanut cultivars through conventional breeding, marker-assisted breeding, or biotechnological methods by gene manipulation. Four samples were analyzed with four hybs. Two samples were obtained from resistant (C20) and and susceptible (TF) cultivars. Two factors were varied in the experimental design: (i) peanut cultivars (resistant (GT-C20) and susceptible (TF)) and (ii) Aspergillus exposure. A combination of these factors produced four hybridizations as follows: (1) C20Y vs. TFY (GT-C20 infected vs. TF infected) (2) C20Y vs. C20N (GT-C20 infected vs. not infected) (3) TFY vs. TFN (TF infected vs. not infected) (4) C20N vs. TFN (GT-C20 not infected vs. TF not infected)
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Project description:The emergence of Candida auris poses a significant health challenge that has led to a new era of multidrug-resistant fungal infections. Invasive infections caused by C. auris are usually associated with remarkable morbidity and mortality. For many years, amphotericin B (AmB) remained the most efficient and the last line of treatment against most hard-to-treat fungal infections. However, strains of C. auris possess extraordinary resistance to most antifungal agents, including AmB. In this study, we screened ~2600 FDA-approved drugs and clinical compounds to identify the antiemetic drug rolapitant as a promising enhancer to AmB against C. auris. Rolapitant exhibited potent synergistic interactions with AmB against all tested (29/29) C. auris isolates. In a time-kill assay, rolapitant restored the fungicidal activity of AmB within 4 h. Additionally, the synergistic relationship between rolapitant and AmB was observed against other medically crucial Candida, Cryptococcus and Aspergillus species with ΣFICI that ranged from 0.16 to 0.5. In a transcriptomic study, ion transporters and ATP generation were identified as primary pathways impacted in C. auris AR0390 cells exposed to rolapitant. An ATP luminescence assay confirmed that rolapitant, at sub-inhibitory concentrations, significantly interfered with ATP production in C. auris. Moreover, rolapitant enhanced the in vivo activity of AmB in a mouse model of disseminated C. auris infection, as the combination reduced the fungal burden in murine kidneys by ~1 log (~90%) colony forming units. Our findings warrant further investigation of using rolapitant to overcome AmB resistance in C. auris and other fungal species.
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Project description:Summary taken from our paper “Aspergillus terreus Sectorization: A Morphological Phenomenon Shedding Light on Amphotericin B Resistance Mechanism”: WT and ATSec strains were grown in AMM broth for 30 h at 30 °C. Afterwards, the cultures were subjected to either DMSO (control) or 1 µg/ml AmB treatment for 1 h/4 h. Triplicates of each combination of these factors were made, resulting in a total of 24 samples. RNA was extracted with a Promega GmbH kit (Madison, Wisconsin, USA) following the manufacturer’s instructions. The RNA-seq experiment was conducted by BGI, generating a total of around 20 million 100bp paired-end reads with the DNBSEQ platform. BGI employed SOAPnuke (51) to remove rRNA, adaptor-containing sequences, low quality reads, and reads with high unknown nucleotide content, producing "clean reads" datasets that were used in the analysis. On average, clean read datasets contain 45.1 Mb of reads, while the raw read datasets contain 48.7 Mb. For clean reads, the mean Q20 value is 98.3%, and the mean Q30 value is 92.5%.
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