Ontology highlight
ABSTRACT:
PROVIDER: PRJNA954686 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24140629_1.fastq.gz | Fastqsanger.gz | |||
| SRR24140629_2.fastq.gz | Fastqsanger.gz | |||
| SRR24140630_1.fastq.gz | Fastqsanger.gz | |||
| SRR24140630_2.fastq.gz | Fastqsanger.gz | |||
| SRR24140631_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:In a given bacterial population, antibiotic treatment kills a large portion of the population, while a small, tolerant subpopulation survives. Tolerant cells disrupt the efficacy of antibiotic treatment and increase the likelihood that a population gains antibiotic resistance. Antibiotic tolerance is different from resistance because tolerant cells cannot grow and replicate in the presence of the antibiotic, but when the antibiotic is removed, they begin to propagate. When a population becomes resistant, the antibiotic becomes ineffective, which is a major health concern. Since antibiotic tolerance often leads to antibiotic resistance, we have taken a systems biology approach to examine how regulatory networks respond to antibiotic stress so that cells can survive and recover after antibiotic treatment. We have compared gene expression with and without ampicillin in E. coli.
2020-12-04 | GSE156896 | 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: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:<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:Antibiotic treatment typically eliminates a significant portion of a bacterial population, leaving behind a smaller subset of tolerant cells that can survive the treatment. These tolerant cells hinder the effectiveness of the antibiotic, potentially leading to the development of antibiotic resistance within the population. Antibiotic tolerance differs from resistance: tolerant cells are unable to grow or reproduce in the presence of the antibiotic, but they can proliferate once the antibiotic is removed. However, in cases of resistance, the antibiotic loses its efficacy entirely, posing a significant threat to public health. Our study challenges the long-held consensus that persisters are completely dormant and are of one single population. Our results clearly show that persisters are not as dormant as once thought, and multiple populations of persisters form during lethal antibiotic treatment despite the cells being genetically identical. We compared the transcriptome profiles at different time points to investigate the dynamic changes and/or existence of multiple persister subpopulations in response to lethal antibiotic ampicillin (Amp) and ciprofloxacin (Cip) treatment in E. coli.
2024-06-21 | GSE256167 | GEO
Project description:The rise of antimicrobial resistant pathogens calls for new antibacterial treatments, but potent new compounds are scarce. Development of new antibiotics is difficult, especially against Gram-negative bacteria, as here uptake is strongly hindered by the additional outer membrane. Most antimicrobial agents against Gram-negatives use the porin mediated pathway to cross the outer membrane, which limits the choice of an antibiotic, as it has to fit by size, charge and hydrophilicity. In E. coli, the major porins OmpF and OmpC are associated with antibiotic translocation and therefore also with unspecific antibiotic cross-resistance. In this regard, alternative uptake routes are of interest. We were interested in the uptake opportunities of the small, natural product antibiotic negamycin and thereby found new uptake pathways across the outer membrane of E. coli. Besides OmpF and OmpC, we investigated the role of the minor porins OmpN and ChiP in negamycin translocation. We detected an effect of OmpN and ChiP on negamycin susceptibility and confirmed passage by electrophysiological assays. The structure of OmpN was resolved in order to analyze the negamycin translocation mechanism by computational simulations. As abundancy of these minor porins was low in E. coli, their transcript levels were analyzed by RNA-Seq. Increased transcripts levels of ompN and chiP were observed upon negamycin treatment, hinting at a role in antibiotic uptake. These new, additional uptake pathways across the outer membrane of E. coli highlight the antibiotic potential of negamycin, especially as resistance development is low due to availability of multiple uptake routes at both the outer and inner membranes
2023-10-01 | GSE183363 | GEO
Project description:Understanding constraints which shape antibiotic resistance is key for predicting and controlling drug resistance. Here, we performed high-throughput laboratory evolution of Escherichia coli. The transcriptome, resistance, and genomic profiles for the evolved strains in 48 environments were quantitatively analyzed. By analyzing the quantitative datasets through interpretable machine learning techniques, the emergence of low dimensional phenotypic states within the 192 strains was observed. Further analysis revealed the underlying biological processes responsible for the distinct states. We also report a novel constraint which leads to decelerated evolution. These findings bridge the genotypic, gene expression, and drug resistance space, and lead to a comprehensive understanding of constraints for antibiotic resistance.
2020-10-12 | GSE137348 | GEO
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:Escherichia coli laboratory strains remain instrumental to the discovery and development of biomarkers as drugs and diagnostic analytes in the post genomic era. The transcriptional regulator SlyA is a member of the multiple antibiotic resistance regulator family of transcription factors, which is associated with bacterial responses to host-derived oxidative stress, antibiotics resistance and virulence, and homologues exist in other Enterobacteriaceae. Here, we announce a transcriptome RNA sequencing data set detailing global gene expression in the wild type E. coli BW25113 and the slyA mutant. Results reveal heterogeneous functionality of SlyA that may vary between pathovars of E. coli. but which require further annotations of differentially expressed tRNAs
2021-03-16 | GSE168963 | GEO
Project description:Bacterial evolution of antibiotic resistance frequently has deleterious side effects on microbial growth, virulence, and susceptibility to other antimicrobial agents. However, it is unclear how these trade-offs could be utilized for manipulating antibiotic resistance in the clinic, not least because the underlying molecular mechanisms are poorly understood. Using laboratory evolution, we demonstrate that clinically relevant resistance mutations in Escherichia coli constitutively rewire a large fraction of the transcriptome in a repeatable and stereotypic manner. Strikingly, lineages adapted to functionally distinct antibiotics and having no resistance mutations in common show a wide range of parallel gene expression changes that alter oxidative stress response, iron homeostasis, and the composition of the bacterial outer membrane and cell surface. These common physiological alterations are associated with changes in cell morphology and enhanced sensitivity to antimicrobial peptides. Finally, the constitutive transcriptomic changes induced by resistance mutations are largely distinct from those induced by antibiotic stresses in the wild-type. This indicates a limited role for genetic assimilation of the induced antibiotic stress response during resistance evolution. Our work suggests that diverse resistance mutations converge on similar global transcriptomic states that shape genetic susceptibility to antimicrobial compounds.
2023-01-26 | GSE223493 | GEO