Context-specific action of macrolide antibiotics on the eukaryotic ribosome
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ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE164275 | GEO | 2021/05/25
REPOSITORIES: GEO
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Project description:Context-specific action of macrolide antibiotics on the eukaryotic ribosome
| PRJNA689836 | ENA
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: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: Not available
| S-EPMC8121947 | biostudies-literature
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
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. The design utilized an available two color microarray slide for the entire transcriptome of Campylobacter jejuni. Four hybridizations were performed each with independently extracted samples of either macrolide susceptible ATCC 700819 cDNA samples or its isogenic Eryr transformant T.L.101 cDNA samples. A dye swap was utilized to help minimize dye dependent bias. Thus, there were four biological replicates of each sample.
2011-11-02 | E-GEOD-33330 | biostudies-arrayexpress
Project description:Campylobacter, a major foodborne pathogen, is increasingly resistant to macrolide antibibotics. previous findings suggeted that development of macrolide resistance in campylobacter requires a multi-step process, but the molecular mechanisms involved in the process are not known. In our study, multiple seriess of macrolide-resistant C. jejuni mutants were selected in vitro by stepwise exposure of C. jejuni 81-176 to increasing concentrations of erythromycin and tylosin. A set of the selected resistance were subjected to microarray and the the global transcriptional profile was analyzed. In this sery, DNA microarray was used to compare the gene expression profiles of macrolide resistant strains (76E2, 76E8 and 76E64) with its parent wild-type strain C. jejuni 81-176. This assay identified a large number of genes that showed >1.5 fold changes (q-value<0.1) in expression in the macrolide resistant strains. The up-regulated genes are involved in surface structure,ribosomal, heat shock and some specific Misc memerbrane , while the majority of the down-regulated genes are involved in energy metabolism, amino acid biosynthesis. The over-expression of genes involved in surface structure and Misc memerbrance was associated with the development of intermedial-level resistance to macrolide in campylobacter 81-176. Keywords:intermedial-level macrolide resistant C. jejuni selected from C. jejuni 81-176. step-wise selection.
2010-12-28 | GSE17899 | GEO
Project description:Campylobacter, a major foodborne pathogen, is increasingly resistant to macrolide antibibotics. previous findings suggeted that development of macrolide resistance in campylobacter requires a multi-step process, but the molecular mechanisms involved in the process are not known. In our study, multiple seriess of macrolide-resistant C. jejuni mutants were selected in vitro by stepwise exposure of C. jejuni 81-176 to increasing concentrations of erythromycin and tylosin. A set of the selected resistance were subjected to microarray and the the global transcriptional profile was analyzed. In this sery, DNA microarray was used to compare the gene expression profiles of macrolide resistant strains (76E2, 76E8 and 76E64) with its parent wild-type strain C. jejuni 81-176. This assay identified a large number of genes that showed >1.5 fold changes (q-value<0.1) in expression in the macrolide resistant strains. The up-regulated genes are involved in surface structure,ribosomal, heat shock and some specific Misc memerbrane , while the majority of the down-regulated genes are involved in energy metabolism, amino acid biosynthesis. The over-expression of genes involved in surface structure and Misc memerbrance was associated with the development of intermedial-level resistance to macrolide in campylobacter 81-176. Keywords:intermedial-level macrolide resistant C. jejuni selected from C. jejuni 81-176. step-wise selection. The design utilized an available two color microarray slide for the entire transcriptome of Campylobacter jejuni. Four hybridizations were performed each with independently extracted samples of either macrolide susceptible C. jejuni 81-176 cDNA samples or macrolide resistant C. jejuni cDNA samples. A dye swap was utilized to help minimize dye dependent bias. Thus there were three to four biological replicates of each sample.
2010-12-28 | E-GEOD-17899 | biostudies-arrayexpress
Project description:Campylobacter, a major foodborne pathogen, is increasingly resistant to macrolide antibibotics. Previous findings suggeted that development of macrolide resistance in campylobacter requires a multi-step process, but the molecular mechanisms involved in the process are not known. In our study, multiple series of macrolide-resistant C. jejuni mutants were selected in vitro by stepwise exposure of C. jejuni NCTC11168 to increasing concentrations of erythromycin and tylosin. A set of the selected resistance were subjected to microarray and the the global transcriptional profile was analyzed. In this sery, DNA microarray was used to compare the gene expression profiles of macrolide resistant strains (68E1, 68E8 and 68E64) with its parent wild-type strain NCTC11168. The assay identified a small number of genes that showed significant changes (q-value<0.1) in expression in the low-level macrolide resistant strain 68E1, while a large number of gene showing significant changes in intermedia-level resistant stran 68E8 and high-level resistant strain 68 E64. The up-regulated genes in the resistant strains are involved in miscellaneous periplasmic proteins, efflux protienand putative aminotransferase, while the majority of the down-regulated genes are involved in electron transport,lipoprotein, heat shock protein and unknown function proteins. These findings suggest that there is not much change in low-level macrolide resistant C. jejuni strain. The over-expression of efflux pump and periplasmic protein was involved in the development of resistance to macrolide in C. jejuni. Keywords: macrolide resistant C. jejuni selected from NCTC 11168 step-wise selection.
2010-12-28 | GSE17881 | GEO
Project description:RNA-seq based transcriptome profiling allows a detailed molecular analysis of the E.coli transcriptome (~4200 genes) after perturbation with different antibiotics. Transcriptome fingerprints enable the identification of gene and pathway level responses to treatment to derive a mechanistic understanding of antibiotics mode of action and to differentiate antibiotics. For this goal, treatment has to be performed in a short time period and with sublethal concentrations of the antibiotics. Sublethal concentrations were chosen based on the EC90 concentration of the antibiotic necessary to change the cellular morphology compared to control conditions. Conclusions: Our study represents the first detailed analysis of E.coli transcriptomes after treatment with different antibiotics, with biologic replicates, generated by RNA-seq technology. The experimental design and data analysis reported here should provide a framework for comparative investigations of expression profiles of known and novel antibiotics. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions.
2019-03-25 | GSE110137 | GEO