Ontology highlight
ABSTRACT:
PROVIDER: PRJNA845125 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19537086_1.fastq.gz | Fastqsanger.gz | |||
| SRR19537086_2.fastq.gz | Fastqsanger.gz | |||
| SRR19537087_1.fastq.gz | Fastqsanger.gz | |||
| SRR19537087_2.fastq.gz | Fastqsanger.gz | |||
| SRR19537088_1.fastq.gz | Fastqsanger.gz |
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Project description:Objectives: Development of daptomycin resistance (DAPR) in Staphylococcus aureus is associated with clinical treatment failures. Mechanism(s) of such resistance has not been clearly defined. Methods: We studied an isogenic daptomycin-susceptible (DAPS) and daptomycin-resistant (DAPR) S. aureus strain pair (616; 701) from a patient with relapsing endocarditis during daptomycin treatment, using comparative transcriptomic and proteomic techniques. Results. Minor differences in genome content were found between strains by DNA hybridization. Transcriptomic analyses identified a number of genes differentially expressed in important functional categories: cell division, metabolism of bacterial envelopes and global regulation. Of note, the DAPR isolate exhibited reduced expression of the major cell wall autolysis gene coincident with upregulation of genes involved in wall teichoic acid production. Using quantitative (q)RT-PCR on gene cadre putatively involved in cationic peptide resistance, we formulated a putative regulatory network compatible with microarray data-sets, mainly implicating bacterial envelopes. Of interest, qRT-PCR of this same gene cadre from two distinct isogenic DAPS/DAPR clinical strain pairs revealed evidence of other strain dependent networks operative in the DAPR phenotype. Comparative proteomics of 616 vs 701 revealed differential abundance of proteins in various functional categories including: cell-wall associated targets and biofilm-formation proteins. Phenotypically, strains 616 and 701 showed major differences in ability to develop bacterial biofilms in presence of the antibacterial lipid, oleic acid. Conclusions: Compatible with previous in vitro observations, in vivo acquired DAPR in S. aureus is a complex, multistep phenomenon allowing for: i) strain dependent phenotypes; ii) transcriptome adaptation; and iii) modification of lipid and protein content of cellular envelopes. Daptomycin suceptible strain vs daptomycin non suceptible strain after daptomycin treatment
2011-12-02 | E-GEOD-28632 | biostudies-arrayexpress
Project description:Swiss VRE ST612 with reduced daptomycin susceptibility
| PRJEB80474 | ENA
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:The study aims to identify genes associated with daptomycin resistance.
2011-04-08 | GSE26249 | GEO
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:Clostridioides difficile is a Gram-positive opportunistic pathogen that results in 220,000 infections, 12,000 deaths, and upwards of $1 billion in medical costs in the US each year. C. difficile is highly resistant to a variety of antibiotics, but we have a poor understanding of how C. difficile senses and responds to antibiotic stress, and how such sensory systems affect clinical outcomes. There has been recent interest in using a daptomycin analog, Surotomycin, to treat C. difficile infections. We have identified a spontaneous C. difficile mutant that displays increased daptomycin resistance. We performed whole-genome sequencing that this mutant possessed a nonsense mutation, S605*, in draS which encodes a putative sensor histidine kinase of a two-component system (TCS). The draSS605* mutant has approximately a 4-8-fold increase in daptomycin MIC compared to WT. We found that expression of constitutively active DraRD54E in WT increases daptomycin resistance 8-16-fold and increases bacitracin resistance ~4-fold. We found that a selection of lipid II inhibiting compounds leads to increased activity of the luciferase-based reporter, PdraR-sLucopt including vancomycin, bacitracin, ramoplanin, and daptomycin. Using RNA-seq we identified the DraRS regulon. Interestingly, we found that DraRS can induce expression of the previously identified hex locus required for synthesis of a novel glycolipid produced in C. difficile. Our data suggest that induction of the hex locus by DraR explains some, but not all, of the DraR-induced daptomycin and bacitracin resistance.
2023-06-17 | GSE234961 | GEO
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:The study aims to identify genes associated with daptomycin resistance. Samples were hybridized on aminosilane coated slides with 70-mer oligos.
2011-04-08 | E-GEOD-26249 | biostudies-arrayexpress