Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1058990 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The study aims to identify genes associated with Linezolid resistance. Linezolid resistant strains were compared to a Linezolid sensitive reference strain in the presence of linezolid and absence of linezolid (mock).
2011-04-08 | GSE26358 | GEO
Project description:In this study, we investigated the role of efflux pump genes in linezolid resistance. M. tuberculosis H37Rv cultures were exposed to sub-inhibitory concentrations of linezolid (¼ MIC) for 24 hours, and transcriptomic analysis was performed to identify upregulated genes. Of the 120 genes involved in cell wall processes, 9/120 (7.5%) were efflux pump genes, primarily belonging to the ATP-binding cassette (ABC), major facilitator superfamily (MFS), resistance nodulation division (RND), and small multidrug resistance (SMR) families. qRT-PCR, performed at 1/2, 1/4 and 1/8 MIC of linezolid, confirmed the RNA-seq results, showing that 8/9 (88.88%) of the efflux pump genes were upregulated at 1/8 MIC of linezolid, indicating that this concentration is optimal for studying efflux pump activity. These findings not only identify 1/8 MIC as optimum concentration for efflux pump studies after linezolid exposure, they also highlight the significant role of efflux pumps in linezolid resistance, providing potential targets for further research on efflux pumps in clinical isolates of M. tuberculosis.
2025-02-20 | GSE288598 | GEO
Project description:The translation inhibitor Linezolid is an important antibiotic of last resort against multiresistant gram-positive pathogens including MRSA. Linezolid is reported to specifically inhibit extracellular virulence factors, but the molecular cause is unknown. To elucidate the physiological response of S. aureus to Linezolid in general and the possible inhibition of virulence factors specifically we performed a holistic study. We added Linezolid to logarithmically growing S. aureus cells and analyzed the Linezolid stress response with transcriptomics, quantitative proteomics and microscopy experiments. As previously observed in studies on other translation inhibitors S. aureus is adapting its protein biosynthesis machinery to the reduced translation efficiency, for example the synthesis of ribosomal proteins is induced. But we also observed unexpected results like a general decline in the amount of extracellular and membrane proteins. In addition cell shape and size changed after Linezolid stress and cell division was diminished. Finally, the chromosome condensed after LZD stress and lost contact to the membrane.
2016-02-22 | GSE65209 | GEO
Project description:The translation inhibitor Linezolid is an important antibiotic of last resort against multiresistant gram-positive pathogens including MRSA. Linezolid is reported to specifically inhibit extracellular virulence factors, but the molecular cause is unknown. To elucidate the physiological response of S. aureus to Linezolid in general and the possible inhibition of virulence factors specifically we performed a holistic study. We added Linezolid to logarithmically growing S. aureus cells and analyzed the Linezolid stress response with transcriptomics, quantitative proteomics and microscopy experiments. As previously observed in studies on other translation inhibitors S. aureus is adapting its protein biosynthesis machinery to the reduced translation efficiency, for example the synthesis of ribosomal proteins is induced. But we also observed unexpected results like a general decline in the amount of extracellular and membrane proteins. In addition cell shape and size changed after Linezolid stress and cell division was diminished. Finally, the chromosome condensed after LZD stress and lost contact to the membrane. sample versus pool design (pool = mixture of equal amounts of all RNA samples analyzed), all RNA samples were isolated as biological triplicates
2016-02-22 | E-GEOD-65209 | biostudies-arrayexpress
Project description:Background: Beyond its role as a ribosome-targeting antibiotic, linezolid was recently shown to modulate immune responses by inhibiting mitochondrial translation. Since mitochondrial dysfunction is implicated in various fibrotic diseases, including systemic sclerosis (SSc), this study aimed to evaluate the antifibrotic potential of linezolid and delineate its underlying mechanisms in SSc. Methods: The effects of linezolid on fibrotic tissue remodeling were assessed using multiple experimental systems: human dermal fibroblasts, human macrophages, three-dimensional SSc skin equivalents (SScSE), the murine model of sclerodermatous chronic graft-versus-host disease (sclGvHD) and precision-cut skin slices (PCSS) obtained from SSc patients, by RNA sequencing, immunofluorescence, Western Blot and histology. Mitochondrial function was evaluated using Seahorse assays alongside mitochondrial protein synthesis assessments. Results: Linezolid inhibited TGFβ-induced fibroblast activation in cultured human fibroblasts, SScSE, sclGvHD mice and SSc PCSS, as demonstrated by reversal of profibrotic gene expression programs, downregulation of TGFβ, WNT, and JAK-STAT signaling and by reductions in αSMA expression or stress fiber formation, which led to reduced collagen deposition and ameliorated skin or lung fibrosis in vivo. Mechanistically, linezolid induced metabolic alterations by inhibiting mitochondrial translation in fibroblasts to hamper the oxidative phosphorylation, reduce the NAD⁺/NADH ratio and downregulate glycolysis, an essential metabolic pathway for fibroblast activation. Conclusions: This study provides first evidence that inhibiting mitochondrial translation with linezolid ameliorates fibrotic tissue remodeling. Since linezolid is already clinically approved as a reserve antibiotic, these findings hold translational promise and support the use of linezolid as a novel treatment for fibrotic disorders after further validation.
2026-01-29 | GSE310202 | GEO
Project description:We report the context-specific activity of two peptidyl transferase targeting antibiotics, chloramphenicol and linezolid. By generating ribosome profiling data in the presence or absence of either chloramphenicol or linezolid we mapped the relative change of ribosome density induced by these antibiotics. We find that both inhibitors preferentially arrest ribosomes that carry either an alanine, serine, or threonine in the penultimate (-1) position of the nascent peptide chain. Additionally ribosomes that carry a glycine in either the P site (0) or A-site (+1) counteract the inhibitory activity of both inhibitors. The context-specific action of chloramphenicol illuminates the operation of the mechanism of inducible resistance that relies on programmed drug-induced translation arrest. In addition, our findings expose the functional interplay between the nascent chain and the peptidyl transferase center.
2016-09-08 | GSE86536 | GEO
Project description:The precise mechanism and effects of antibiotics in host gene expression and immunomodulation in MRSA infection is unknown. Using a well characterized Methicillin Resistant Staphylococcus aureus (MRSA) isolate USA300 in a murine model of infection, we determined that linezolid and vancomycin induced differential production of bacterial toxins and host cytokines, differences in host gene expression, and differences in immunomodulators during MRSA bloodstream infection. A total of 35 A/J mice, categorized into seven groups (no infection; no infection with linezolid; no infection with vancomycin; 2 hour post-infection (hpi) S. aureus; 24 hpi S. aureus; 24 hpi S. aureus with linezolid; and 24 hpi S. aureus with vancomycin), were used in this study. Mice were injected with USA300 (6 x 106 CFU/g via i.p. route), then intravenously treated with linezolid (25 mg/kg) or vancomycin (25 mg/kg) at 2 hpi. Control and S. aureus infected mice were euthanized at each time point (2 h or 24h) following injection. Whole blood RNA was used for microarray; three cytokines and two S. aureus toxins [PantonValentine Leukocidin (PVL) and alpha hemolysin] were quantified in mouse serum by ELISA. S. aureus CFUs were significantly reduced in blood and kidney after linezolid or vancomycin treatment in S. aureus-infected mice. In vivo IL-1M-NM-2 in mouse serum was significantly reduced in both linezolid (p=0.001) and vancomycin (p=0.006) treated mice compared to untreated ones. IL-6 was significantly reduced only in linezolid treated (p<0.001) but not in vancomycin treated mice. However, another proinflammatory cytokine, TNF-M-NM-1, did not exhibit altered levels in either linezolid or vancomycin treated mice (p=0.3 and p=0.51 respectively). In vivo level of bacterial toxin, Panton-Valentine leukocidin, in mouse serum was significantly reduced only in linezolid treated mice (p=0.02) but not in vancomycin treated mice. There was no significant effect of either treatment in in vivo level of alpha hemolysin production. Unsupervised hierarchical clustering using the gene expression data from 35 microarrays revealed distinct clustering based on infection status and treatment group. Study of the antibiotic-specific difference in gene expression identified the number of genes uniquely expressed in response to S. aureus infection, infection with linezolid treatment, and infection with vancomycin treatment. Pathway associations study for the differentially expressed genes in each comparison group (Control vs. 24 h S. aureus infection, 24 h S. aureus infection vs. 24 h S. aureus linezolid, and 24 h S. aureus infection vs. 24 h S. aureus vancomycin) in mice using Kyoto Encyclopedia of Genes and Genomes (KEGG) identified toll-like receptor signaling pathway to be common to every comparison groups studied. Glycerolipid metabolism pathway was uniquely associated only with linezolid treatment comparison group. The findings of this study provide the evidence that protein synthesis inhibitor like linezolid does a better job in treating MRSA sepsis compared to cell wall acting antibiotics like vancomycin. To identify differences in host gene expression in a murine sepsis model treated with a) linezolid and b) vancomycin, we used whole blood gene expression (RNA) signatures from A/J inbred mice infected with USA 300 MRSA to evaluate differences in host gene expression among mice treated with linezolid and vancomycin. We used 5 RNA samples from MRSA-infected, linezolid- or vancomycin-treated mice. A total of 7 experimental groups have been employed: 1) Uninfected control group: (negative controls). 2) Uninfected, linezolid-treated group: Uninfected, linezolid-treated mice. 3) Uninfected vancomycin-treated group: Uninfected, vancomycin-treated mice. 4) Infected control group (positive control 2 h) MRSA-infected, untreated mice. 5) Infected control group (positive control 24 h): MRSA-infected, untreated mice. 6) Infected linezolid group: MRSA-infected, linezolid-treated mice. 7) Infected vancomycin group: MRSA-infected, vancomycin-treated mice.
2014-06-05 | E-GEOD-38531 | biostudies-arrayexpress
Project description:Background: Bacterial small regulatory RNAs (sRNAs) have been implicated in important processes including antimicrobial stress response. However, the full extent of sRNA involvement in antimicrobial response in Staphylococcus aureus, an important pathogen, is incompletely understood. We investigated the transcriptional profiles of a linezolid-resistant, livestock-associated methicillin-resistant S. aureus (LA-MRSA) strain ST398 under conditions of linezolid stress. Methods: Cells in mid-exponential growth were subjected to low (8 µg/ml) and high (16 µg/ml) dose linezolid treatments followed by high throughput RNA sequencing. Read mapping and differential expression analysis were performed followed by detection and interrogation of various sRNA and mRNA transcripts. Results: Twenty-three putative regulatory RNA transcripts were expressed under low- and high-dose exposure conditions. Cis-acting regulatory elements, mainly targeting ribosomal biogenesis constituted the majority of transcriptional response with limited antisense and small RNA expression. Conclusions: This is the first study to investigate linezolid-responsive small RNA transcription in LA-MRSA strain ST398 and the first to query regulatory RNAs on a background of linezolid resistance. It provides preliminary insights and a basis for interrogating small RNAs in other strains in the quest to understand drug-responsive regulatory RNAs and identify potential anti-staphylococcal therapeutic candidates.
2025-09-30 | GSE272244 | GEO
Project description:Transcriptional profiling of Mycobacterium tuberculosis H37Rv strains comparing control DMSO treated strains with Linezolid treated strains. Goal was to determine the effects of Linezolid against Mycobacterium tuberculosis H37Rv strains. Two-condition experiment,control DMSO treated strains vs. Linezolid treated strains. Biological replicates: 2 control replicates, 2 Linezolid replicates.
2011-10-10 | E-GEOD-32718 | biostudies-arrayexpress