Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1271731 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33821529_1.fastq.gz | Fastqsanger.gz | |||
| SRR33821529_2.fastq.gz | Fastqsanger.gz | |||
| SRR33821530_1.fastq.gz | Fastqsanger.gz | |||
| SRR33821530_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:Drug resistance and tolerance eliminate the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. To uncover antibiotic tolerance mechanisms in biofilms, we applied stable isotope labeling with amino acids (SILAC) proteomics to selectively label and compare proteomes of sensitive and tolerant subpopulations of biofilms formed by Pseudomonas aeruginosa towards colistin, a 'last-resort' antibiotic against multidrug-resistant Gram-negative pathogens. Migration was essential in forming colistin-tolerant biofilm subpopulations, as colistin-tolerant cell-aggregates migrated with type IV pili, onto the top of killed biofilm. The colistin-tolerant cell-aggregates employed quorum sensing (QS) to initiate the formation of fresh colistin-tolerant subpopulations, highlighting multicellular behavior in antibiotic tolerance development. Erythromycin treatment which inhibits motility and QS, boosted biofilm eradication by colistin. This novel ‘-omics’ strategy to study antibiotic tolerant cells provides key insights for designing novel treatments against infections unsuppressed by conventional antimicrobials.
2016-02-16 | PXD002369 | Pride
Project description:Acinetobacter baumannii is often highly resistant to multiple antimicrobials, posing a risk of treatment failure, and colistin is a "last resort" for treatment of the bacterial infection. However, colistin resistance is easily developed when the bacteria are exposed to the drug, and a comprehensive analysis of colistin-mediated changes in colistin-susceptible and -resistant A. baumannii is needed. In this study, using an isogenic pair of colistin-susceptible and -resistant A. baumannii isolates, alterations in morphologic and transcriptomic characteristics associated with colistin resistance were revealed. Whole-genome sequencing showed that the resistant isolate harbored a PmrBL208F mutation conferring colistin resistance, and all other single-nucleotide alterations were located in intergenic regions. Using scanning electron microscopy, it was determined that the colistin-resistant mutant had a shorter cell length than the parental isolate, and filamented cells were found when both isolates were exposed to the inhibitory concentration of colistin. When the isolates were treated with inhibitory concentrations of colistin, more than 80% of the genes were upregulated, including genes associated with antioxidative stress response pathways. The results elucidate the morphological difference between the colistin-susceptible and -resistant isolates and different colistin-mediated responses in A. baumannii isolates depending on their susceptibility to this drug.
2025-05-02 | GSE267612 | GEO
Project description:Objectives: Carbapenem-resistant Acinetobacter baumannii (CRAB) are one of the most difficult pathogen to treat. The only drug recently approved by the FDA that is active against CRAB is cefiderocol. However, recent studies have shown higher all-cause mortality rate in the group of patients treated with cefiderocol, that may be due to heteroresistance, a phenotype characterized by the survival of a small proportion of cells in a population seemingly isogenic. Previous studies showed that adding human fluids to CRAB cultures can lead to CFDC heteroresistance. To better understand the nature of this phenomenon, we carried out molecular and phenotypic analyses of CRAB heteroresistant bacterial subpopulations. Methods: The CRAB strain AMA40 was cultured in the presence of cefiderocol and human pleural fluid (HPF) to isolate heteroresistant variants. Two of them, AMA40 IHC_1 and IHC_2, were subjected to whole genome sequencing and transcriptomic analysis to identify the mutations and transcriptomic changes responsible for the development of cefiderocol resistance. The impact of mutations on the pharmacodynamic activity of cefiderocol was assessed by susceptibility testing, EDTA and Boronic acid inhibition analysis, biofilm formation, and static time-kill assays. Results: Variants AMA40 IHC_1 and IHC_2 had 53 mutations, forty of which were common to both heteroresistant strains. None of the mutations are located inside genes associated with iron-uptake systems or β-lactam resistance. However, pipA, a gene associated with iron homeostasis in other species, was mutated in heteroresistant strains. Transcriptomic analyses revealed modifications in levels of expression of genes associated with antibiotic resistance. The blaNDM-1, blaADC-2, pbp3, and pbp1 were expressed at higher levels. At the same time, the carO and ompA genes’ expression was reduced. Collateral resistance to amikacin was observed in the heteroresistant variants. Static time-kill assays showed that when CA-MHB was supplemented with human serum albumin, the main protein component of HPF, cefiderocol killing activity was considerably reduced in all three strains. Conclusions: We conclude that heteroresistance to cefiderocol in CRAB, when exposed to fluids containing high HSA, is caused by mutations and modifications in the expression of genes associated with resistance to β-lactams.
2023-03-31 | E-MTAB-12444 | biostudies-arrayexpress
Project description:Klebsiella pneumoniae clinical isolates, OXA48 and Wt, colistin heteroresistance
| PRJEB66360 | ENA
Project description:We found that the antibiotic colistin acts synergistically with antifungals of the echinocandin class (e.g. aminocandin) on C. albicans cells. In order to elucidate the mode of action of colistin in fungi we performed microarray analysis of samples treated with only aminocandin (0.00125µg/ml) or treated with aminocandin (0.00125µg/ml) and colistin (5µg/ml). We compared: (A). untreated cells to cells treated with aminocandin only; (B). cells treated with aminocandin to cells treated with aminocandin and colistin (which is the focus of this experiment). By comparing those datasets it should be possible to identify genes differentially expressed in response to aminocandin and in response to both drugs. And subsequently to be able to interpret where in the cell colistin acts. (See related experiment in ArrayExpress: E-MEXP-3437 for comparison between untreated cells vs cells treated with aminocandin only.)
2012-03-03 | E-MEXP-3438 | biostudies-arrayexpress
Project description:Colistin is a crucial last-line drug used for the treatment of life-threatening infections caused by multi-drug resistant strains of the Gram-negative bacteria, Acinetobacter baumannii. However, colistin resistant A. baumannii isolates can be isolated following failed colistin therapy. Resistance is most often mediated by the addition of phosphoethanolamine (pEtN) to lipid A by PmrC, following missense mutations in the pmrCAB operon encoding PmrC and the two-component signal transduction system PmrA/PmrB. We recovered an isogenic pair of A. baumannii isolates from a single patient before (6009-1) and after (6009-2) failed colistin treatment that displayed low/intermediate and high levels of colistin resistance, respectively. To understand how increased colistin-resistance arose, we genome sequenced each isolate which revealed that 6009-2 had an extra copy of the insertion sequence element ISAba125 within a gene encoding an H-NS-family transcriptional regulator. Consequently, transcriptomic analysis of the clinical isolates identified was performed and more than 150 genes as differentially expressed in the colistin-resistant, hns mutant, 6009-2. Importantly, the expression of eptA, encoding a second lipid A-specific pEtN transferase, but not pmrC, was significantly increased in the hns mutant. This is the first time an H-NS-family transcriptional regulator has been associated with a pEtN transferase and colistin resistance.
2018-02-19 | GSE107964 | GEO
Project description:To investigate the mechanism of PmB resistance and heteroresistance in Enterobacter bugandensis by analysing the differential gene expression under PmB treatment.
2024-05-01 | GSE218614 | GEO
Project description:Hematopoietic stem cells (HSCs) constitute a rare cell population in bone-marrow and are capable of live-long self-renewal and production of all mature blood cell types. Cell differentiation processes are governed by epigenetic mechanisms whose study during early differentiation steps will provide insights into stem cell function and differentiation. We performed whole-genome bisulfite sequencing on HSCs and their immediate progeny, namely three different multipotent progenitor subpopulations (MPP1, MPP2, and MPP). Whole-genome bisulfite sequencing of hematopoietic stem cells (HSCs) and 3 different multipotent progenitor subpopulations (MPP). Three independent biological replicates each were analyzed.
2014-08-25 | E-GEOD-52709 | biostudies-arrayexpress