Ontology highlight
ABSTRACT:
PROVIDER: PRJNA435557 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6761710_1.fastq.gz | Fastqsanger.gz | |||
| SRR6761710_2.fastq.gz | Fastqsanger.gz | |||
| SRR6761711_1.fastq.gz | Fastqsanger.gz | |||
| SRR6761711_2.fastq.gz | Fastqsanger.gz | |||
| SRR6761712_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Several groups have shown that through evolution experiments, tolerance and resistance evolved rapidly under cyclic antibiotic treatment. In other words, intermittent antibiotic exposure performed in a typical adaptive laboratory evolution (ALE) experiments will “train” the bacteria to become tolerant/resistant to the drug. Using this experimental strategy, we performed in vitro laboratory evolution in MRSA using daptomycin, and mine novel daptomycin tolerance and resistance mutants, which were isolated at specific time points during the evolution experiments. Three daptomycin-tolerant isolates with different tolerance level were generated from our laboratory evolution (TOL2 and TOL5 with a mild-tolerance phenotype, and TOL6 with a high-tolerance phenotype). They all bear mutations at different genes, and have no increase in MIC towards daptomycin. Besides, we also isolated three daptomycin-resistant isolates (RES1, RES2, RES3) that have a single point mutation in the same gene, mprF, but at different locations, leading to an increased MIC towards daptomycin. Through proteomics, we uncovered the differential adaptation strategies of these daptomycin tolerant and resistant MRSA strains, and how they respond differently to antibiotics compared to the ancestral wild-type.
2022-07-14 | PXD026741 | Pride
Project description:Evolution of antibiotic resistance in microbes is frequently achieved by acquisition of spontaneous mutations during antimicrobial therapy. Here we demonstrate that inactivation of a central regulator of iron homeostasis (fur) facilitates laboratory evolution of ciprofloxacin resistance in Escherichia coli. To decipher the underlying molecular mechanisms, we first performed a global transcriptome analysis and demonstrated a substantial reorganization of the Fur regulon in response to antibiotic treatment. We hypothesized that the impact of Fur on evolvability under antibiotic pressure is due to the elevated intracellular concentration of free iron and the consequent enhancement of oxidative damage-induced mutagenesis. In agreement with expectations, over-expression of iron storage proteins, inhibition of iron transport, or anaerobic conditions drastically suppressed the evolution of resistance, while inhibition of the SOS response-mediated mutagenesis had no such effect in fur deficient population. In sum, our work revealed the central role of iron metabolism in de novo evolution of antibiotic resistance, a pattern that could influence the development of novel antimicrobial strategies. We used microarrays to identify genotype specific transcriptional changes under severe DNA damaging conditions (antibiotic ciprofloxacin). We treated Escherichia coli cells with a highly toxic level of ciprofloxacin (gyrase inhibitor) for RNA extraction and hybridization on Affymetrix microarrays. We planned to find genotype specific transcriptional responses using WT control (BW25113) and fur-knockout mutant (selected from the KEIO collection) strains during antibiotic treatments. For each treatment type we used two biological replicates.
2014-09-11 | E-GEOD-55662 | biostudies-arrayexpress
Project description:Several groups have shown that through evolution experiments, tolerance and resistance evolved rapidly under cyclic antibiotic treatment. In other words, intermittent antibiotic exposure performed in a typical adaptive laboratory evolution (ALE) experiments will “train” the bacteria to become tolerant/resistant to the drug. Although ALE has added new knowledge regarding the impact of varying treatment conditions on the evolution of tolerance/resistance, the role of some parameters such as population bottlenecks remains poorly understood. In this study, we employed ALE to investigate the evolution of methicillin-resistant S. aureus under repetitive daptomycin treatment using a modified protocol that incorporated population bottleneck following antibiotic exposure. We observed that although tolerance development is slower under bottlenecking conditions, the populations finally attained tolerance mutation in the yycH gene after twelve cycles of treatment. Extending the evolution experiment and changing the treatment scheme to a fast evolution protocol (treatment during exponential phase without bottlenecking) led to the emergence of daptomycin resistance (mutation in mprF gene). Through proteomics, we uncovered the differential adaptation strategies of these daptomycin tolerant and resistant MRSA strains, and how they respond differently to antibiotics compared to the ancestral wild-type.
2022-07-16 | PXD031078 | Pride
Project description:Understanding constraints which shape antibiotic resistance is key for predicting and controlling drug resistance. Here, we performed high-throughput laboratory evolution of Escherichia coli. The transcriptome, resistance, and genomic profiles for the evolved strains in 48 environments were quantitatively analyzed. By analyzing the quantitative datasets through interpretable machine learning techniques, the emergence of low dimensional phenotypic states within the 192 strains was observed. Further analysis revealed the underlying biological processes responsible for the distinct states. We also report a novel constraint which leads to decelerated evolution. These findings bridge the genotypic, gene expression, and drug resistance space, and lead to a comprehensive understanding of constraints for antibiotic resistance.
2020-10-12 | GSE137348 | GEO
Project description:Evolution of antibiotic resistance in microbes is frequently achieved by acquisition of spontaneous mutations during antimicrobial therapy. Here we demonstrate that inactivation of a central regulator of iron homeostasis (fur) facilitates laboratory evolution of ciprofloxacin resistance in Escherichia coli. To decipher the underlying molecular mechanisms, we first performed a global transcriptome analysis and demonstrated a substantial reorganization of the Fur regulon in response to antibiotic treatment. We hypothesized that the impact of Fur on evolvability under antibiotic pressure is due to the elevated intracellular concentration of free iron and the consequent enhancement of oxidative damage-induced mutagenesis. In agreement with expectations, over-expression of iron storage proteins, inhibition of iron transport, or anaerobic conditions drastically suppressed the evolution of resistance, while inhibition of the SOS response-mediated mutagenesis had no such effect in fur deficient population. In sum, our work revealed the central role of iron metabolism in de novo evolution of antibiotic resistance, a pattern that could influence the development of novel antimicrobial strategies. We used microarrays to identify genotype specific transcriptional changes under severe DNA damaging conditions (antibiotic ciprofloxacin).
2014-09-11 | GSE55662 | GEO
Project description:Understanding constraints which shape antibiotic resistance is key for predicting and controlling drug resistance. Here, we performed high-throughput laboratory evolution of Actinobacillus pleuropneumoniae and its ciprofloxacin resistance-inducing derivatives.This study aims to explore the mechanism of acquired ciprofloxacin resistance in Actinobacillus pleuropneumoniae.
2021-10-06 | GSE181030 | GEO
Project description:Background: Antibiotic resistance is an urgent threat to public health. Prior to the evolution of antibiotic resistance, bacteria frequently undergo response and tend to develop a state of adaption to the antibiotic. Ciprofloxacin is a broad-spectrum antibiotic by damaging DNA. With the widespread clinical application, the resistance of bacteria to ciprofloxacin continues to increase. This study aimed to investigate the transcriptome changes under the action of high concentration of ciprofloxacin in Escherichia coli. Results: We identified 773 up-regulated differentially expressed genes (DEGs) and 645 down-regulated DEGs in ciprofloxacin treated cells. Enriched biological pathways reflected the up-regulation of biological process such as DNA damage and repair system, toxin/antitoxin systems, formaldehyde detoxification system, peptide biosynthetic process and cellular protein metabolic process. With KEGG pathway analysis, up-regulated DEGs of kdsA and waa operon were associated with “LPS biosynthesis”. rfbABC operon was related to “streptomycin biosynthesis” and “polyketide sugar unit biosynthesis ”. Down-regulated DEGs of thrABC and fliL operons were associated with “flagellum-dependent cell motility” and “bacterial-type flagellum” in GO terms, and enriched into “biosynthesis of amino acids” and “flagellar assembly” in KEGG pathways. After treatment of ciprofloxacin, bacterial lipopolysacchride (LPS) release was increased by two times, and the mRNA expression level of LPS synthesis genes, waaB, waaP and waaG were elevated (P < 0.05). Conclusions: Characterization of the gene clusters by RNA-seq showed high dose of ciprofloxacin not only lead to damage of bacterial macromolecules and components, but also induce protective response against antibiotic action by up-regulating the SOS system, toxin/antitoxin system and formaldehyde detoxification system. Moreover, genes related to biosynthesis of LPS were also upregulated by the treatment indicating that ciprofloxacin can enhance the production of endotoxin on the level of transcription. These results demonstrated that transient exposure of high dose ciprofloxacin is double edged. Cautions should be taken when administering the high dose antibiotic treatment for infectious diseases.
2020-06-16 | GSE152445 | GEO
Project description:Bacterial evolution of antibiotic resistance frequently has deleterious side effects on microbial growth, virulence, and susceptibility to other antimicrobial agents. However, it is unclear how these trade-offs could be utilized for manipulating antibiotic resistance in the clinic, not least because the underlying molecular mechanisms are poorly understood. Using laboratory evolution, we demonstrate that clinically relevant resistance mutations in Escherichia coli constitutively rewire a large fraction of the transcriptome in a repeatable and stereotypic manner. Strikingly, lineages adapted to functionally distinct antibiotics and having no resistance mutations in common show a wide range of parallel gene expression changes that alter oxidative stress response, iron homeostasis, and the composition of the bacterial outer membrane and cell surface. These common physiological alterations are associated with changes in cell morphology and enhanced sensitivity to antimicrobial peptides. Finally, the constitutive transcriptomic changes induced by resistance mutations are largely distinct from those induced by antibiotic stresses in the wild-type. This indicates a limited role for genetic assimilation of the induced antibiotic stress response during resistance evolution. Our work suggests that diverse resistance mutations converge on similar global transcriptomic states that shape genetic susceptibility to antimicrobial compounds.
2023-01-26 | GSE223493 | GEO
Project description:Pseudomonas aeruginosa infections can be virtually impossible to eradicate and the evolution of resistance during antibiotic therapy is a significant concern. In this study, we use DNA microarrays to characterize the global transcriptional response of P. aeruginosa to clinical-like doses of the antibiotic ciprofloxacin and also to determine the component that is regulated by LexA cleavage and the SOS response. We find that genes involved in virtually every facet of metabolism are down-regulated in response to ciprofloxacin. The LexA-controlled SOS regulon identified by microarray analysis includes only fifteen genes, but does include several genes that encode proteins involved in recombination and replication, including two inducible polymerases known to play a role in mutation and the evolution of antibiotic resistance in other organisms. The data suggests that the inhibition of LexA cleavage during therapy might help combat this pathogen by decreasing its ability to adapt and evolve resistance. Keywords: Time course of response of P. aeruginosa to the antibiotic ciprofloxacin
2006-08-04 | GSE5443 | GEO