Antibiotic resistant gene amplification
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ABSTRACT:
PROVIDER: PRJEB42285 | ENA |
REPOSITORIES: ENA
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Project description:We investigated the influence of genome position on propensity to amplify. First, we integrated a mutant form of DHFR into different positions in the human genome, challenged cells with methotrexate and then studied the genomic alterations arising in drug resistant cells. We observed site specific differences in methotrexate sensitivity, organization of amplicons and amplification frequency. One site was uniquely associated with a significantly enhanced propensity to amplify and recurrent amplicon boundaries, possibly implicating a rare folate sensitive fragile site in initiating amplification. Hierarchical clustering of gene expression patterns and subsequent gene enrichment analysis revealed two clusters differing significantly in expression of MYC target genes independent of integration site. We introduced a mutant form of DHFR (L22F), which confers greater resistance to methotrexate than the wild type (endogenous) gene into HCT116+chr3 cells and isolated independent clones containing DHFR* at different positions in the genome and identified genome sequences flanking the integration site of DHFR* using inverse PCR. For further analysis, we selected only clones, which were considered to have a single insertion of DHFR* by inverse PCR (13 independent insertion sites). The individual insertion site clones were further characterized with respect to genome copy number profiles. To select methotrexate resistant colonies, we exposed cells to a concentration of methotrexate that was three to four times the IC-50 for each integration site. Genomic copy number profiles were obtained for isolated resistant colonies (GSE6262) by using UCSF HumArray platform (GPL4421). Twelve methotrexate resistant colonies (four different integration sites) were selected for microarray analysis of gene expression at the mRNA level. The untreated integration site clone was used as the reference (Cy5 labeled cDNA) for each of the hybridizations with its respective resistant colonies (Cy3 labeled cDNA). Hybridizations were carried out on arrays of printed long oligonucleotides (70mers) containing 21,000 elements (Operon V2.0, printed in J. David Gladstone Institutes, Genomics Core Laboratory).
2007-10-08 | E-GEOD-6361 | biostudies-arrayexpress
Project description:Analysis of Antibiotic Resistant Organisms recovered from Clinical and Environmental Sources in Manitoba, Canada Genome sequencing and assembly
| PRJNA511988 | ENA
Project description:We investigated the influence of genome position on propensity to amplify. First, we integrated a mutant form of DHFR into different positions in the human genome, challenged cells with methotrexate and then studied the genomic alterations arising in drug resistant cells. We observed site specific differences in methotrexate sensitivity, organization of amplicons and amplification frequency. One site was uniquely associated with a significantly enhanced propensity to amplify and recurrent amplicon boundaries, possibly implicating a rare folate sensitive fragile site in initiating amplification. Hierarchical clustering of gene expression patterns and subsequent gene enrichment analysis revealed two clusters differing significantly in expression of MYC target genes independent of integration site. Keywords: Gene amplification, array CGH, chromosomal fragile sites
2007-10-08 | GSE6361 | GEO
Project description:Phage-plasmids produce antibiotic resistant lysogens
| PRJEB52357 | ENA
Project description:The aim of this experiment was to determine if the development of resistance to antibiotics can be driven by the concentration and speciation of Cu. Experimental setup was designed to investigate two hypotheses for which two strains of Gram- bacteria have been selected: - Do TE enhance AR in resistant bacteria? Resistant strain: Bioluminescent Pseudomonas aeruginosa PAO1 (Xen41, Tetracycline resistant) - Do TE induce AR in sensitive bacteria? Sensitive strain: Pseudomonas aeruginosa PAO1 (Wild Type)
2020-10-28 | GSE160188 | GEO
Project description:The occurrence, prevalence and fate of antibiotic resistant genes and microbial community in Ili river
| PRJEB49834 | ENA
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:Antibiotic-resistant bacteria can escape from the killing of host immune and settle in the host to form persistent infections. In this study, we investigated the environmental adaptation mechanism of resistant Staphyloccus aureus (S. aureus) to host environment by Data-independent acquisition based quantitative proteomics and functional validation. The detection of growth curve and MIC indicated that ciprofloxacin-resistant S. aureus (Cip-R) showed survival advantage over sensitive strain. Cip-R also exhibited stronger adhesion and invasion ability than sensitive bacteria. Cip-R stimulation resulted in the production of stronger inflammatory factors of the host cells. Proteomics study combined with biochemical validations showed that Cip-R obtains adaptability to host via up-regulation of TCA cycle and down-regulation of ribosome metabolism and protein folding to maintain energy to support their survival. Thus, this study will help us to further explain the growth strategy of resistant bacteria to adapt to the host environment, and provide important information for the development of new antibacterial drugs.
2022-05-31 | PXD029584 | Pride
Project description:The response of antibiotic adapted resistant mutants of B. cenocepacia J2315 to antibiotic stress was investigated using expression profiling of three biological replicates and comparing the profiles to the J2315 parent control grown without antibiotics.<br>A reference design was used with Cy3 labeled genomic DNA of B. cenocepacia J2315 as common reference. Three test conditions with three biological replicates each were compared to three replicates of the control condition.<br>Test conditions: J2315-A grown in the presence of 250 ug per ml amikacin, J2315-M grown in the presence of 8 ug per ml meropenem and J2315-T grown in the presence of 60 ug per ml trimethoprim and 300 ug per ml sulfamethoxazole.<br>Control condition: J2315 parent strain grown without antibiotics.
2010-08-12 | E-MEXP-2708 | biostudies-arrayexpress
Project description:Amplifications, regions of focal high level copy number change, lead to overexpression of oncogenes or drug resistance genes in tumors. Their presence is often associated with poor prognosis; however the use of amplification as a mechanism for overexpression of a particular gene in tumors varies. To investigate the influence of genome position on propensity to amplify, we integrated a mutant form of DHFR into different positions in the human genome, challenged cells with methotrexate and then studied the genomic alterations arising in drug resistant cells. We observed site specific differences in methotrexate sensitivity, organization of amplicons and amplification frequency. One site was uniquely associated with a significantly enhanced propensity to amplify and recurrent amplicon boundaries, possibly implicating a rare folate sensitive fragile site in initiating amplification. Hierarchical clustering of gene expression patterns and subsequent gene enrichment analysis revealed two clusters differing significantly in expression of MYC target genes independent of integration site. These studies suggest that genome context together with the particular challenges to genome stability experienced during the progression to cancer contribute to the propensity to amplify a specific oncogene or drug resistance gene, whereas the overall functional response to drug (or other) challenge may be independent of the genomic location of an oncogene. Keywords: Gene amplification, array CGH, chromosomal fragile sites
2007-10-08 | GSE6262 | GEO