Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1037603 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Conjugative plasmids are the main vehicle for the horizontal spread of antimicrobial resistance (AMR). Although AMR plasmids provide advantages to their hosts under antibiotic pressure, they can also disrupt the cell’s regulatory network, impacting the fitness of their hosts. Despite the importance of plasmid-bacteria interactions on the evolution of AMR, the effects of plasmid carriage on host physiology has remained underexplored, and most studies have focused on model bacteria and plasmids that lack clinical relevance. Here, we analyzed the transcriptional response of 11 clinical enterobacterial strains (2 Escherichia coli, 1 Citrobacter freundii and 8 Klebsiella spp.) and the laboratory-adapted E. coli MG1655 to carriage of pOXA-48, one of the most widely spread carbapenem-resistance plasmids. Our analyses revealed that pOXA-48 produces variable responses on their hosts, but commonly affects processes related to metabolism, transport, response to stimulus, cellular organization and motility. More notably, the presence of pOXA-48 caused an increase in the expression of a small chromosomal operon of unknown function in Klebsiella spp. and C. freundii, which is not present in E. coli. Phylogenetic analysis suggested that this operon has been horizontally mobilized across different Proteobacteria species. We demonstrate that a pOXA-48-encoded LysR transcriptional regulator controls the expression of the operon in Klebsiella spp. and C. freundii. In summary, our results highlight a crosstalk between pOXA-48 and the chromosome of its natural hosts.
2024-07-16 | GSE269852 | GEO
Project description:<p>The study of antimicrobial resistance (AMR) in infectious diarrhea has generally been limited to cultivation, antimicrobial susceptibility testing and targeted PCR assays. When individual strains of significance are identified, whole genome shotgun (WGS) sequencing of important clones and clades is performed. Genes that encode resistance to antibiotics have been detected in environmental, insect, human and animal metagenomes and are known as "resistomes". While metagenomic datasets have been mined to characterize the healthy human gut resistome in the Human Microbiome Project and MetaHIT and in a Yanomani Amerindian cohort, directed metagenomic sequencing has not been used to examine the epidemiology of AMR. Especially in developing countries where sanitation is poor, diarrhea and enteric pathogens likely serve to disseminate antibiotic resistance elements of clinical significance. Unregulated use of antibiotics further exacerbates the problem by selection for acquisition of resistance. This is exemplified by recent reports of multiple antibiotic resistance in Shigella strains in India, in Escherichia coli in India and Pakistan, and in nontyphoidal Salmonella (NTS) in South-East Asia. We propose to use deep metagenomic sequencing and genome level assembly to study the epidemiology of AMR in stools of children suffering from diarrhea. Here the epidemiology component will be surveillance and analysis of the microbial composition (to the bacterial species/strain level where possible) and its constituent antimicrobial resistance genetic elements (such as plasmids, integrons, transposons and other mobile genetic elements, or MGEs) in samples from a cohort where diarrhea is prevalent and antibiotic exposure is endemic. The goal will be to assess whether consortia of specific mobile antimicrobial resistance elements associate with species/strains and whether their presence is enhanced or amplified in diarrheal microbiomes and in the presence of antibiotic exposure. This work could potentially identify clonal complexes of organisms and MGEs with enhanced resistance and the potential to transfer this resistance to other enteric pathogens.</p> <p>We have performed WGS, metagenomic assembly and gene/protein mapping to examine and characterize the types of AMR genes and transfer elements (transposons, integrons, bacteriophage, plasmids) and their distribution in bacterial species and strains assembled from DNA isolated from diarrheal and non-diarrheal stools. The samples were acquired from a cohort of pediatric patients and controls from Colombia, South America where antibiotic use is prevalent. As a control, the distribution and abundance of AMR genes can be compared to published studies where resistome gene lists from healthy cohort sequences were compiled. Our approach is more epidemiologic in nature, as we plan to identify and catalogue antimicrobial elements on MGEs capable of spread through a local population and further we will, where possible, link mobile antimicrobial resistance elements with specific strains within the population.</p>
| phs001260 | dbGaP
Project description:The Sfh protein is encoded by self-transmissible plasmids involved in human typhoid and is closely related to the global regulator H-NS. We have found that Sfh provides a stealth function that allows the plasmids to be transmitted to new bacterial hosts with minimal effects on their fitness. Introducing the plasmid without the sfh gene imposes a mild H-NS- phenotype and a severe loss of fitness due to titration of the cellular pool of H-NS by the A+T-rich plasmid. This stealth strategy seems to be used widely to aid horizontal DNA transmission and has important implications for bacterial evolution.
2007-01-15 | E-SGRP-7 | biostudies-arrayexpress
Project description:The presence of Donor-Specific anti-HLA Antibodies (DSA) is associated with an increased risk of both acute and chronic antibody-mediated rejection (AMR) in kidney allografts. AMR has remained challenging in kidney transplantation and is the major cause of late allograft loss. However, not all patients with DSA develop AMR, leading to the question of whether this represents accommodation, if other protective mechanisms exist or if this is actually a state of pre-rejection. Clinical and histological features, and gene expression profiles of kidney biopsy and blood samples of donor-specific antibody (DSA)+ patients without rejection were compared to antibody-mediated rejection (AMR) patients to elucidate the mechanisms involved in prevention of AMR. Of the 71 DSA+ patients, 46 had diagnosis of AMR and 25 did not show rejection. 50 DSA- patients without rejection were used as control. A subgroup of patients with available biopsy (n=61) and blood samples (n=54) were analyzed by microarrays. Both, DSA+/AMR+ and DSA+/AMR- biopsies showed increased expression of gene transcripts associated with cytotoxic T, natural killer cells, macrophages, interferon-gamma and rejection compared to DSA- biopsies. Regulatory T cell transcripts were up-regulated in DSA+/AMR+ and B cell transcripts in DSA+/AMR- biopsies. Whole blood gene expression analysis showed increased immune activity in only DSA+/AMR+ patients. There were no differentially expressed tolerant genes studied (n=14) in the blood or biopsy specimens of DSA+/AMR- patients. During a median 36 months follow-up, 4 DSA+/AMR- patients developed AMR, 12 continued to have DSAs but 9 lost DSAs. Gene expression profiles did not predict the development of AMR or persistence of DSAs. These results indicate increased immune activity in DSA+/AMR- biopsies despite lack of histologic findings of rejection.
2013-08-23 | GSE50084 | GEO
Project description:The presence of Donor-Specific anti-HLA Antibodies (DSA) is associated with an increased risk of both acute and chronic antibody-mediated rejection (AMR) in kidney allografts. AMR has remained challenging in kidney transplantation and is the major cause of late allograft loss. However, not all patients with DSA develop AMR, leading to the question of whether this represents accommodation, if other protective mechanisms exist or if this is actually a state of pre-rejection. Clinical and histological features, and gene expression profiles of kidney biopsy and blood samples of donor-specific antibody (DSA)+ patients without rejection were compared to antibody-mediated rejection (AMR) patients to elucidate the mechanisms involved in prevention of AMR. Of the 71 DSA+ patients, 46 had diagnosis of AMR and 25 did not show rejection. 50 DSA- patients without rejection were used as control. A subgroup of patients with available biopsy (n=61) and blood samples (n=54) were analyzed by microarrays. Both, DSA+/AMR+ and DSA+/AMR- biopsies showed increased expression of gene transcripts associated with cytotoxic T, natural killer cells, macrophages, interferon-gamma and rejection compared to DSA- biopsies. Regulatory T cell transcripts were up-regulated in DSA+/AMR+ and B cell transcripts in DSA+/AMR- biopsies. Whole blood gene expression analysis showed increased immune activity in only DSA+/AMR+ patients. There were no differentially expressed tolerant genes studied (n=14) in the blood or biopsy specimens of DSA+/AMR- patients. During a median 36 months follow-up, 4 DSA+/AMR- patients developed AMR, 12 continued to have DSAs but 9 lost DSAs. Gene expression profiles did not predict the development of AMR or persistence of DSAs. These results indicate increased immune activity in DSA+/AMR- biopsies despite lack of histologic findings of rejection. All clinically indicated kidney transplant biopsies performed at our institution after January 2009 were reviewed and 263 patients with anti-HLA antibody testing at the time of biopsy were identified. There were 71 DSA+ and 192 DSA- patients (Figure 1). Of the 71 DSA+ patients, 46 had biopsy diagnosis of acute AMR (n=9) or chronic AMR (n=37), and 25 had normal histopathology or minimal non-specific interstitial fibrosis/tubular atrophy (IFTA). Of the 192 DSA- patients, 50 patients with normal histology and/or mild non-specific IFTA were used as a control group. Clinical and histopathological findings of these 3 groups (DSA+/AMR+, DSA+/AMR- and DSA-) were analyzed. A subgroup of patients who were enrolled in the Institutional Review Board-approved âImmune Monitoring Studyâ who had clinically indicated biopsy (n=61) and whole blood samples (n=54) stored were used for genomic analysis. Twenty-eight biopsy and blood samples from DSA+/AMR+ patients, 13 biopsy and 14 blood samples from DSA+/AMR- patients, and 20 biopsy and 12 blood samples from DSA- patients, were available for microarray analysis.
2013-08-23 | E-GEOD-50084 | biostudies-arrayexpress
Project description:Here we have compared adult wildtype (N2) C. elegans gene expression when grown on different bacterial environments/fod sources in an effort to model naturally occuring nematode-bacteria interactions at the Konza Prairie. We hypothesize that human-induced changes to natural environments, such as the addition of nitrogen fertalizer, have effects on the bacterial community in soils and this drives downstream changes in the structure on soil bacterial-feeding nematode community structure. Here we have used transcriptional profiling to identify candidate genes involved in the interaction of nematodes and bacteria in nature.
2009-05-02 | GSE15923 | GEO
Project description:HEK293T cells were transfected with the Rbp1-amr or slow (R729H-amr) α-amanitin resistant subunit of RNA Pol II and selected with α-amanitin 24 hours after transfection for additional 24 hours. Total RNA was extracted and global changes in gene expression were determined using microarray chips. MiRNAs are transcribed by RNA pol II but the transcriptional features influencing their synthesis are poorly defined. Here we report that a TATA-box in miRNA and a subset of protein-coding genes is associated with increased sensitivity to a slow rate of transcription elongation. We also show that promoters driven by TATA-box or NF-κB elicit high transcription re-initiation rate, but paradoxically lower levels of miRNA. Interestingly, miRNA synthesis was converted to a more productive mode by decreasing initiation rate, but less productive when the re-initiation rate increased. This phenomenon was found to be associated with a delay in miR-146a induction by NF-κB. We also demonstrate that miRNAs are remarkably strong pause sites. Our findings suggest that lower efficiency of miRNA synthesis directed by the TATA-box or NF-κB is a consequence of frequent transcription initiation that lead to Pol II crowding at pause sites, thereby increasing the chance of collision and premature termination. These findings highlight the importance of the transcription initiation mechanism for miRNA synthesis, and have implications for TATA-box promoters in general. HEK293T cells were transfected with plasmids directing the expression of α-amanitin-resistant variants of Pol II (Rpb1-amr and R749H-amr). α-amanitin was added and RNA was prepared 24 and 48 h later, respectively. The data provided is from 3 Rpb1-amr vs 3 R749H-amr (6 samples).
2013-07-01 | E-GEOD-48163 | biostudies-arrayexpress
Project description:Tuberculosis (TB) is an ancient disease caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb). The rise of antimicrobial resistance (AMR) threatens to bring Mtb to the forefront of bacterial pathogens as the current treatments are increasingly becoming ineffective. Understanding the development of AMR and the virulence processes of Mtb is crucial for the identification of new drug targets and the rational design of anti-TB treatments. One of the established mechanisms of resistance is through the function of efflux proteins, which are transmembrane transporters that bind and remove antibiotic molecules out from the cell. Here, we determine the role of Rv3728, a major facilitator superfamily (MFS) efflux pump protein, which also predicted to bind 3',5'-cyclic adenosine monophosphate (cAMP). Using bioinformatic tools and cAMP binding assay, we confirm that Rv3728 binds to cAMP and identified E597 and R606 as important residues involved in binding. Although Rv3728 deletion has no impact on bacterial resistance and tolerance to different antibiotics, it affects membrane permeability and alters the acylation profile of phosphatidyl-myo-inositol mannosides lipids.
2024-06-10 | GSE268977 | GEO
Project description:YAV20 (E7946 loxP[dciA] SpR lacZ::cre ZeoR), AB14 (YAV20 inv[glmU-mioC]) and AB23 ( YAV20 ΔrecB::CmR) were created by natural transfromation using cognate plasmids. Cells were grown in the M( minimla media supplemented with fructose, with or without arabinose (ara). Genomic DNA was extracted with the Sigma GenElute® bacterial genomic DNA kit to generate a genomic library according to Illumina’s protocol. The libraries and the sequencing were performed by the High-throughput Sequencing facility of the I2BC (https://www.i2bc.paris-saclay.fr/sequencing/ng-sequencing/, CNRS, Gif-sur-Yvette, France). Genomic DNA libraries were made with the ‘Nextera DNA library preparation kit’ (Illumina) following the manufacturer’s recommendations.
2024-02-14 | E-MTAB-12729 | biostudies-arrayexpress