Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR272374_1.fastq.gz | Fastqsanger.gz | |||
| ERR272374_2.fastq.gz | Fastqsanger.gz |
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Project description:Pseudomonas aeruginosa is an opportunistic pathogen known to cause both acute and chronic infections. P. aeruginosa often encounters hypoxic/anoxic environments within the host, which increases its tolerance to many conventional antibiotics. Towards identifying novel therapeutic treatments, we have been exploring the potential of chlorate, a pro-drug that kills hypoxic/anoxic, antibiotic-tolerant P. aeruginosa populations. Chlorate kills P. aeruginosa when it is enzymatically reduced by hypoxically-induced nitrate reductase, thereby generating the toxic oxidizing agent, chlorite. To better assess its therapeutic potential, we investigated mechanisms of chlorate toxicity and resistance in P. aeruginosa. We combined transposon mutagenesis and high-throughput sequencing to identify genes that alter P. aeruginosa fitness during chlorate treatment. We found that methionine sulfoxide reductase (msr) genes, whose products repair oxidized methionine residues, support survival during chlorate stress. We showed that chlorate treatment leads to proteome-wide methionine oxidation, which is exacerbated in a ∆msrA∆msrB strain. Highly abundant proteins were the likeliest targets of methionine oxidation, including proteins that are abundant under standard conditions (e.g. ribosomes) and proteins that increase in abundance in response to chlorate stress (e.g. protein chaperones). The addition of exogenous methionine partially rescued P. aeruginosa survival during chlorate treatment, suggesting that widespread methionine oxidation contributes to cell death. Finally, we found that decreased nitrate reductase activity is a common mechanism of chlorate resistance. Because nitrate respiration likely sustains P. aeruginosa anaerobic growth and survival within the host, developing chlorate resistance would be expected to hinder pathogen fitness in such environments.
2023-10-24 | PXD033396 | Pride
Project description:Primary objectives: The primary objective is to investigate circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Primary endpoints: circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
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Project description:The study investigated the ability of selected (hyper-)thermophilic prokaryotes to grow anaerobically by the reduction of perchlorate and chlorate. Physiological, genomic and proteome analyses suggest that the Crenarchaeon Aeropyrum pernix reduces (per)chlorate with a periplasmic enzyme related to nitrate reductases, while it lacks a functional chlorite-disproportionating enzyme (Cld). A. pernix seems to rely on the chemical reactivity of reduced sulfur compounds with the toxic intermediate chlorite to complete the pathway. The chemical oxidation of thiosulfate (in excessive amounts present in the medium) to sulfate and the concomitant release of chloride anions from the reduction of chlorite are the products of a biotic-abiotic (per)chlorate reduction pathway in A. pernix. The apparent absence of Cld in two other (per)chlorate-reducing microorganisms and their dependence on sulfide for (per)chlorate reduction is consistent with earlier-made observations on (per)chlorate-reducing Archaeoglobus fulgidus. All here discussed microorganisms use strategies for complete (per)chlorate reduction that differ from the physiology of classical (per)chlorate-reducing mesophiles.
2017-06-02 | PXD001683 | Pride
Project description:Alicycliphilus denitrificans is a versatile, ubiquitous, facultative anaerobic bacterium. A. denitrificans strain BC can use chlorate, nitrate and oxygen as electron acceptor for growth. Cells display a prolonged lag-phase when transferred from nitrate to chlorate and vice versa. Furthermore, cells adapted to aerobic growth do not easily use nitrate or chlorate as electron acceptor. We further investigated these responses of strain BC by differential proteomics, transcript analysis and enzyme activity assays. In nitrate-adapted cells transferred to chlorate and vice versa, appropriate electron acceptor reduction pathways need to be activated. In oxygen-adapted cells, adaptation to the use of chlorate or nitrate is likely difficult due to the poorly active nitrate reduction pathway and low active chlorate reduction pathway. We deduce that the Nar-type nitrate reductase of strain BC also reduces chlorate, which may result in toxic levels of chlorite if cells are transferred to chlorate. Furthermore, the activities of nitrate reductase and nitrite reductase appear to be not balanced when oxygen-adapted cells a shifted to nitrate as electron acceptor, leading to the production of a toxic amount of nitrite. These data suggest that strain BC encounters metabolic challenges in environments with fluctuations in the availability of electron acceptors. Proteomic samples were prepared from Alicycliphilus denitrificans grown in the presence of different electron acceptors: chlorate, nitrate and oxygen. Proteins were separated by a short SDS gel and for each sample 4 in-gel digest slices were prepared. Peptide samples were measured by nLC LTQ-Orbitrap and the data were analysed with MaxQuant using default settings (1% FDR on peptide and protein level) and filtered extra to keep only proteins identified with at least 2 peptides and 1 unique and 1 unmodified peptide.
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Project description:The study is intended to collect specimens to support the application of genome analysis technologies, including large-scale genome sequencing. This study will ultimately provide cancer researchers with specimens that they can use to develop comprehensive catalogs of genomic information on at least 50 types of human cancer. The study will create a resource available to the worldwide research community that could be used to identify and accelerate the development of new diagnostic and prognostic markers, new targets for pharmaceutical interventions, and new cancer prevention and treatment strategies. This study will be a competitive enrollment study conducted at multiple institutions.
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Project description:Single-molecule read technologies allow for detection of epigenomic base modifications during routine sequencing by analysis of kinetic data during the reaction, including the duration between base incorporations at the elongation site (the "inter-pulse duration.") Methylome data associated with a closed de novo bacterial genome of Salmonella enterica subsp. enterica serovar Javiana str. CFSAN001992 was produced and submitted to the Gene Expression Omnibus. Single-sample sequencing and base modification detection of cultured isolate of a foodborne pathogen.
2013-03-15 | E-GEOD-45178 | biostudies-arrayexpress
Project description:Denitrifiers, perchlorate and sulfate reducers
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Project description:Denitrifiers and sulfate reducers Metagenome
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