Ontology highlight
ABSTRACT:
PROVIDER: PRJNA910842 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22674500_1.fastq.gz | Fastqsanger.gz | |||
| SRR22674500_2.fastq.gz | Fastqsanger.gz | |||
| SRR22674600_1.fastq.gz | Fastqsanger.gz | |||
| SRR22674600_2.fastq.gz | Fastqsanger.gz | |||
| SRR22674501_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. 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:Gene copy-number variation, which provides the raw material for the evolution of novel genes, is surprisingly widespread in natural populations. Experimental evolution studies have demonstrated an extremely high spontaneous rate of origin of gene duplications. When organisms are suboptimally adapted to their environment, gene duplication may compensate for reduced fitness by amplifying promiscuous activity of a gene, or increasing dosage of a suboptimal gene. The overarching goal of this study is to inverstigate whether CNVs constitute a common mechanism of adaptive genetic change during compensatory evolution and to further characterize the role of natural selection in dictating their evolutionary spread at a population-genomic level. Outcrossing populations of C. elegans with low fitness were evolved for >200 generations and the frequencies of CNVs in these populations were analyzed by oligonucleotide array comparative genome hybridization, quantitative PCR, and single-worm PCR. Multiple duplications and deletions were detected in intermediate to high frequencies and several lines of evidence suggest that the changes in frequency were adaptive. 1) Many copy-number changes reached high frequency, were near fixation, or were fixed in a short time. 2) Many independent duplications and deletions in high frequency harbor overlapping regions which likely include genes that are under selection for either higher or lower rates of expression. 3) The size spectrum of deuplications and deletions in the adaptive recovery populations is significantly larger than that of spontaneous copy-number variants in mutation accumulation experiments. This is expected if larger CNVs are more likely to encompass genes that are being selected for altered gene dosage. Out results validate the great potential borne by gene copy-number changes for compensatory evolution and adaptation. Experimental genome evolution of copy-number variants in 25 experimental lines compared to 5 ancestral control lines.
2015-04-15 | E-GEOD-67871 | biostudies-arrayexpress
Project description:Gene copy-number variation, which provides the raw material for the evolution of novel genes, is surprisingly widespread in natural populations. Experimental evolution studies have demonstrated an extremely high spontaneous rate of origin of gene duplications. When organisms are suboptimally adapted to their environment, gene duplication may compensate for reduced fitness by amplifying promiscuous activity of a gene, or increasing dosage of a suboptimal gene. The overarching goal of this study is to inverstigate whether CNVs constitute a common mechanism of adaptive genetic change during compensatory evolution and to further characterize the role of natural selection in dictating their evolutionary spread at a population-genomic level. Outcrossing populations of C. elegans with low fitness were evolved for >200 generations and the frequencies of CNVs in these populations were analyzed by oligonucleotide array comparative genome hybridization, quantitative PCR, and single-worm PCR. Multiple duplications and deletions were detected in intermediate to high frequencies and several lines of evidence suggest that the changes in frequency were adaptive. 1) Many copy-number changes reached high frequency, were near fixation, or were fixed in a short time. 2) Many independent duplications and deletions in high frequency harbor overlapping regions which likely include genes that are under selection for either higher or lower rates of expression. 3) The size spectrum of deuplications and deletions in the adaptive recovery populations is significantly larger than that of spontaneous copy-number variants in mutation accumulation experiments. This is expected if larger CNVs are more likely to encompass genes that are being selected for altered gene dosage. Out results validate the great potential borne by gene copy-number changes for compensatory evolution and adaptation.
2015-04-15 | GSE67871 | GEO
Project description:Cationic antimicrobial peptides (CAPs) are promising novel alternatives to conventional antibacterial agents, but the overlap in resistance mechanisms between small-molecule antibiotics and CAPs is unknown. Does evolution of antibiotic resistance decrease (cross-resistance) or increase (collateral sensitivity) susceptibility to CAPs? We systematically addressed this issue by studying the susceptibilities of a comprehensive set of antibiotic resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic resistant bacteria frequently showed collateral sensitivity to CAPs, while cross-resistance was relatively rare. We identified clinically relevant multidrug resistance mutations that simultaneously elevate susceptibility to certain CAPs. Transcriptome and chemogenomic analysis revealed that such mutations frequently alter the lipopolysaccharide composition of the outer cell membrane and thereby increase the killing efficiency of membrane-interacting antimicrobial peptides. Furthermore, we identified CAP-antibiotic combinations that rescue the activity of existing antibiotics and slow down the evolution of resistance to antibiotics. Our work provides a proof of principle for the development of peptide based antibiotic adjuvants that enhance antibiotic action and block evolution of resistance.
2018-03-29 | GSE96706 | GEO
Project description:Several groups have shown that through evolution experiments, tolerance evolved rapidly under cyclic antibiotic treatment which then promote the emergence of resistance. In other words, intermittent antibiotic exposure will “train” the bacteria to become tolerant to the drug, and then boost the chances for them to become fully resistant. This evolutionary trajectory of evolving tolerance and resistance not only occurs in vitro, but also in clinical patients with MRSA blood infections. Despite the fact that repetitive antibiotic treatment will lead to tolerance and resistance development in bacterial populations, the difference on the evolutionary path between those treated with a single drug and drug combination remains unaddressed. In this study, we monitored the development of tolerance in MRSA by treating them with either daptomycin alone for 2 weeks (Scheme 1), or daptomycin combined with rifampin for two weeks (Scheme 2), in a cyclic manner. In addition, we also investigate another scenario where we treat MRSA cells with daptomycin alone for one week, and subsequently treat them with daptomycin and rifampin combination in the second week (Scheme 3). At the end of the evolution experiment, we observed that the population from Scheme 1 developed tolerance towards daptomycin, the population from Scheme 2 developed both tolerance and resistance towards daptomycin, while the population from Scheme 3 developed tolerance after a week of treatment, but then the tolerance phenotype diminished at the end of the second week due to the drug combination treatment. We subjected them to whole genome sequencing and identified single point mutations that are responsible for the observed phenotype. Through proteomics, we compared the proteome profile of the population evolved from scheme 1 (S1D14), scheme 2 (S2D14) and scheme 3 (S3D14), and we observed that these three populations employ distinct mechanisms to survive antibiotic treatment, suggesting that the treatment strategy for these populations should be tailored depending on the treatment conditions.
2021-07-27 | PXD021667 | 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: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:Chronic Pseudomonas aeruginosa infections evades antibiotic therapy and are associated with mortality in cystic fibrosis (CF) patients. We find that in vitro resistance evolution of P.aeruginosa towards clinically relevant antibiotics leads to phenotypic convergence towards distinct states. These states are associated with collateral sensitivity towards several antibiotic classes and encoded by mutations in antibiotic resistance genes, including transcriptional regulator nfxB. Longitudinal analysis of isolates from CF patients reveals similar and defined phenotypic states, which are associated with extinction of specific sub-lineages in patients. In depth investigation of chronic P.aeruginosa populations in a CF patient during antibiotic therapy revealed dramatic genotypic and phenotypic convergence. Notably, fluoroquinolone-resistant subpopulations harboring nfxB mutations were eradicated by antibiotic therapy as predicted by our in vitro data. This study supports the hypothesis that antibiotic treatment of chronic infections can be optimized by targeting phenotypic states associated with specific mutations to improve treatment success in chronic infections.
2018-10-23 | PXD007972 | Pride
Project description:Many organisms can acclimate to new environments through phenotypic plasticity, a complex trait that can be heritable, subject to selection, and evolve. However, the rate and genetic basis of plasticity evolution remain largely unknown. We experimentally evolved outbred populations of the nematode Caenorhabditis remanei under an acute heat shock during early larval development. When raised in a non-stressful environment, ancestral populations were highly sensitive to a 36.8°C heat shock and exhibited high mortality. However, initial exposure to a non-lethal high temperature environment resulted in significantly reduced mortality during heat shock (hormesis). Lines selected for heat shock resistance rapidly evolved the capacity to withstand heat shock in the native environment without any initial exposure to high temperatures, and early exposure to high temperatures did not lead to further increases in heat resistance. This loss of plasticity would appear to have resulted from the genetic assimilation of the heat induction response in the non-inducing environment. However, analyses of transcriptional variation via RNA-sequencing from the selected populations revealed no global changes in gene regulation correlated with the observed changes in heat stress resistance. Instead, assays of the phenotypic response across a broader range of temperatures revealed that the induced plasticity was not fixed across environments, but rather the threshold for the response was shifted to higher temperatures over evolutionary time. These results demonstrate that apparent genetic assimilation can result from shifting thresholds of induction across environments and that analysis of the broader environmental context is critically important for understanding the evolution of phenotypic plasticity. mRNA profiles of ancestral and two experimentally evolved populations of C. remanei at 20°C or 30°C, 6 replicates/temperature for each population
2014-05-04 | E-GEOD-56510 | biostudies-arrayexpress
Project description:Here we provide, for the first time, a longitudinal study of the prevalence, dynamics, and fixation of gross chromosomal rearrangements, including aneuploidy, in the presence and absence of fluconazole during a well-controlled in vitro evolution experiment. While no aneuploidy was detected in any of the no-drug control populations, in all fluconazole-treated populations analyzed, isochromosome 5L [i(5L)] appeared soon after drug exposure, was associated with increased fitness in the presence of drug, and became fixed in independent populations. In two separate cases, larger supernumerary chromosomes composed of i(5L) attached to other chromosome fragments appeared and were later lost during exposure to the drug. Other aneuploidies, particularly trisomies of the smaller chromosomes (Chr3-7), appeared throughout the evolution experiment, and the rapid accumulation of multiple aneuploid chromosomes per cell coincided with the highest resistance to fluconazole.
2009-12-31 | GSE16423 | GEO