Mycobacteriaceae
Ontology highlight
ABSTRACT:
PROVIDER: PRJDB13569 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| DRR375579_1.fastq.gz | Fastqsanger.gz | |||
| DRR375579_2.fastq.gz | Fastqsanger.gz | |||
| DRR375580_1.fastq.gz | Fastqsanger.gz | |||
| DRR375580_2.fastq.gz | Fastqsanger.gz | |||
| DRR375581_1.fastq.gz | Fastqsanger.gz |
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Project description:Reversibility of macrolide resistance affects long-term treatment outcomes in mycobacterium avium complex pulmonary disease: Retrospective single center cohort study
| PRJDB13569 | ENA
Project description:Background: Mycobacterium avium is an opportunistic pathogen that requires complex multidrug treatment. Macrolides, like clarithromycin, are the cornerstone of treatment, but even macrolide-based treatment regimens have suboptimal outcomes. Combining transcriptomic profiling of macrophages and mycobacteria in an in vitro infection model may increase our understanding of the host-pathogen interaction and the effect of antibiotic treatment. Methods: To investigate the molecular interplay between pathogen and host, we developed an optimized protocol for dual RNA-sequencing of human monocyte-derived macrophages infected with M. avium. Results: Upon phagocytosis, host defense processes including immune activation and pathogen recognition were upregulated, while M. avium upregulated expression of PE/PPE genes, which are important for immune recognition. Clarithromycin did not affect gene regulation of the host; the effect of clarithromycin on M. avium gene expression was very different in RPMI compared to intracellular mycobacteria, likely due to the influence of the host environment on expression of the important regulatory WhiB genes. Conclusions These data identify the distinct stress responses of M. avium upon infection and clarithromycin treatment and underline the importance of taking the intracellular localization and interaction with the host into account when studying antibiotics against intracellular pathogens.
2024-01-01 | GSE213117 | GEO
Project description:Background: Mycobacterium avium complex (MAC) bacteria cause opportunistic infections in humans. Treatment yields cure rates of 60% and is comprised of a macrolide, a rifamycin and ethambutol; and in severe cases amikacin. Mechanisms of antibiotic tolerance remain mostly unknown. To elucidate these mechanisms, we studied the transcriptomic response to antibiotics and investigated the contribution of efflux and amikacin modification to susceptibility. Methods: M. avium was subjected to subinhibitory concentrations of clarithromycin, amikacin, ethambutol and rifampicin followed by RNA sequencing. Based thereupon, we characterized M. avium efflux pumps and performed time-kill kinetic analysis using each antibiotic in combination with the efflux pump inhibitors (EPIs) berberine, verapamil and CCCP to study the role of efflux on susceptibility. Finally, we studied the modification of amikacin by M. avium using metabolomic analysis. Results: Changes in respiratory state and changes in ribosome binding and protein folding likely contribute to clarithromycin and amikacin tolerance, respectively. No clear drug-specific mechanisms of tolerance are found for ethambutol and rifampicin. Of the EPIs, only berberine increased the susceptibility to rifampicin and clarithromycin. Finally, we show that M. avium, in contrast to M. abscessus, is not able to modify amikacin. Conclusion: M. avium likely relies on a combination of drug-specific and generic mechanisms of antibiotic tolerance including changes in respiratory and metabolic state in addition to drug efflux and target modification. Efflux inhibition can increase susceptibility but this effect is EPI and antibiotic specific. Finally, the lack of amikacin modifying activity in M. avium is important for its activity.
2024-01-01 | GSE213116 | GEO
Project description:We performed epidemiological, cytokine, and transcriptomic analyses on a prospective, multi-center cohort of 1,928 severely injured patients. We wished to characterize the relationship of advanced age to clinical outcomes and to transcriptomic responses after severe blunt traumatic injury with hemorrhagic shock.
2015-01-06 | E-GEOD-64711 | biostudies-arrayexpress
Project description:Macrolides are clinically important antibiotics thought to inhibit bacterial growth by impeding the passage of newly synthesized polypeptides through the nascent peptide exit tunnel of the bacterial ribosome. Recent data challenged this view by showing that macrolide antibiotics can differentially affect synthesis of individual proteins. In order to understand the general mechanism of macrolide action, we used genome-wide ribosome profiling and analyzed the redistribution of ribosomes translating highly expressed genes in bacterial cells treated with high concentrations of macrolide antibiotics. The metagene analysis indicated that inhibition of early rounds of translation, which would be characteristic of the conventional view of macrolide action, occurs only at a limited number of genes. Translation of most genes proceeds past the 5' proximal codons and can be arrested at more distal codons when the ribosome encounters specific short sequence motifs. The sequence motifs enriched in the sites of arrest are confined to the nascent peptide residues in the peptidyl transferase center but not to the peptide segments that contact the antibiotic molecule in the exit tunnel. This led to the conclusion that the general mode of macrolide action involves selective inhibition of peptide bond formation between specific combinations of donor and acceptor substrates. Additional factors operating in the living cell but not during in vitro protein synthesis may modulate site-specific action of macrolide antibiotics. Comparing ribosome distribution in bacterial cells treated with macrolide antibiotics against the control cells.
2014-11-03 | E-GEOD-61619 | biostudies-arrayexpress
Project description:Macrolides are clinically important antibiotics thought to inhibit bacterial growth by impeding the passage of newly synthesized polypeptides through the nascent peptide exit tunnel of the bacterial ribosome. Recent data challenged this view by showing that macrolide antibiotics can differentially affect synthesis of individual proteins. In order to understand the general mechanism of macrolide action, we used genome-wide ribosome profiling and analyzed the redistribution of ribosomes translating highly expressed genes in bacterial cells treated with high concentrations of macrolide antibiotics. The metagene analysis indicated that inhibition of early rounds of translation, which would be characteristic of the conventional view of macrolide action, occurs only at a limited number of genes. Translation of most genes proceeds past the 5' proximal codons and can be arrested at more distal codons when the ribosome encounters specific short sequence motifs. The sequence motifs enriched in the sites of arrest are confined to the nascent peptide residues in the peptidyl transferase center but not to the peptide segments that contact the antibiotic molecule in the exit tunnel. This led to the conclusion that the general mode of macrolide action involves selective inhibition of peptide bond formation between specific combinations of donor and acceptor substrates. Additional factors operating in the living cell but not during in vitro protein synthesis may modulate site-specific action of macrolide antibiotics.
2014-11-03 | GSE61619 | GEO
Project description:An International Multi-Center Study to Define the Clinical Utility of Microarray–Based Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study) Established in 2005, the MILE (Microarray Innovations in LEukemia) study research program included 11 participating centers in three continents. This cohort of n=2,096 samples represents data on the retrospective whole-genome analysis phase. This dataset is part of the MILE Study (Microarray Innovations In LEukemia) program, headed by the European Leukemia Network (ELN) and sponsored by Roche Molecular Systems, Inc.
2009-09-30 | GSE13159 | GEO
Project description:An International Multi-Center Study to Define the Clinical Utility of Microarray–Based Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study) Established in 2005, the MILE (Microarray Innovations in LEukemia) study research program included 11 participating centers in three continents. This cohort of n=1,152 samples represents data on the retrospective whole-genome analysis phase. This dataset is part of the MILE Study (Microarray Innovations In LEukemia) program, headed by the European Leukemia Network (ELN) and sponsored by Roche Molecular Systems, Inc.
2009-09-30 | GSE13164 | GEO
Project description:Anal squamous cell carcinoma (ASCC) is an infrequent tumor. Since 70s, treatment of stages II-III consists on a combination of 5-fluorouracil (5FU), mitomycin C (MMC), and radiotherapy. The aim of this study is the identification of biomarkers that allow personalized treatment and improvement of therapeutic outcomes. Forty-six tumor paraffin samples from ASCC patients were analyzed by whole-exome sequencing. Single nucleotide polymorphisms and copy number variants (CNVs) were identified and their relation to disease-free survival (DFS) was studied using BRB Array Tool and Kaplan-Meier analyses. Obtained findings were validated in an independent retrospective cohort of 101 ASCC patients with stages I-III from eleven hospitals within the Multidisciplinary Spanish Digestive Cancer Group (GEMCAD) using qPCR Copy Number Assays. GEMCAD validation cohort was also analyzed using mass spectrometry proteomics to assess the biological features of these tumors.
2023-04-26 | PXD037816 | Pride
Project description:Glioblastoma (GBM) is the most aggressive form of brain cancer, characterized by high recurrence and dismal prognosis. Presently, there is no effective in vitro platform that can rapidly measure complex cellular phenotypic traits and predict patient-specific clinical outcomes. Here, we fabricated and evaluated an in vitro testing platform, Microfluidic Assay for Quantification of Cell Invasion (MAqCI), by screening a panel of 28 patient-derived primary GBM specimens in a blinded multi-institutional retrospective cohort study. We quantified the ability of GBM cells to navigate and squeeze through confined microenvironments that mimic tight perivascular conduits and white matter tracts in the brain parenchyma in vivo, as well as the proliferative capacity of highly motile subpopulations. By combining migratory- and proliferative-based indices, MAqCI correctly categorized patients into short- or long-term survival groups with high sensitivity (84%), specificity (89%), and accuracy (86%), and predicted time to recurrence. In a pilot prospective study, MAqCI classified all 5 patients accurately based on their survival outcomes. Overall, our study suggests that invasive growth is intimately linked with GBM progression and patient outcomes, and reveals the translational potential of MAqCI for personalized GBM care.
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