Ecoli adaptive resistance
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR654976_1.fastq.gz | Fastqsanger.gz | |||
| ERR654976_2.fastq.gz | Fastqsanger.gz | |||
| ERR654977_1.fastq.gz | Fastqsanger.gz | |||
| ERR654977_2.fastq.gz | Fastqsanger.gz | |||
| ERR654978_1.fastq.gz | Fastqsanger.gz |
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Project description:Epigenetic-based regulation of transcriptome in Escherichia coli adaptive antibiotic resistance
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Project description:Surfing motility is a novel form of surface adaptation exhibited by the nosocomial pathogen, Pseudomonas aeruginosa, in the presence of the glycoprotein mucin that is found in high abundance at mucosal surfaces especially the lungs of cystic fibrosis and bronchiectasis patients. Here we investigated the adaptive antibiotic resistance of P. aeruginosa under conditions in which surfing occurs compared to cells undergoing swimming. P. aeruginosa surfing cells were significantly more resistant to several classes of antibiotics including aminoglycosides, carbapenems, polymyxins, and fluroquinolones. This was confirmed by incorporation of antibiotics into growth medium, which revealed a concentration-dependent inhibition of surfing motility that occurred at concentrations much higher than those needed to inhibit swimming. To investigate the basis of resistance, RNA-Seq was performed and revealed that surfing influenced the expression of numerous genes. Included amongst genes dysregulated under surfing conditions were multiple genes from the Pseudomonas resistome, which are known to affect antibiotic resistance when mutated. Screening transposon mutants in these surfing-dysregulated resistome genes revealed that several of these mutants exhibited changes in susceptibility to one or more antibiotics under surfing conditions, consistent with a contribution to the observed adaptive resistance. In particular, several mutants in resistome genes, including armR, recG, atpB, clpS, nuoB, and certain hypothetical genes such as PA5130, PA3576 and PA4292, showed contributions to broad-spectrum resistance under surfing conditions and could be complemented by their respective cloned genes. Therefore, we propose that surfing adaption led to extensive multidrug adaptive resistance as a result of the collective dysregulation of diverse genes.
2018-06-26 | GSE110044 | GEO
Project description:Antibiotic resistance is a growing threat, underscoring the need to understand the underlying mechanisms. Aminoglycosides kill bacteria by disrupting translation fidelity, leading to the synthesis of aberrant proteins. Surprisingly, mutations in fusA, a gene encoding translation elongation factor G (EF-G), frequently confer resistance, even though EF-G neither participates in mRNA decoding nor blocks aminoglycoside binding. Here, we show that EF-G resistance variants selectively slow ribosome movement along mRNA when aminoglycoside is bound. This delay increases the chance that the drug dissociates before misreading occurs. Over several elongation cycles, this selective silencing of drug-bound ribosomes prevents error clusters formation, preserving proteome and membrane integrity. As a result, fusA mutations confer resistance early in treatment by preventing self-promoted aminoglycoside uptake. Translation on drug-free ribosomes remains sufficiently rapid to sustain near-normal bacterial growth. This previously unrecognized resistance mechanism—selective silencing of corrupted targets—reveals a novel antibiotic resistance strategy with potential therapeutic implications.
2025-08-29 | PXD063129 | panorama
Project description:Daptomycin represents a reserve antibiotic effective against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Daptomycin resistance (Dap-R) and clinical treatment failure has been associated with adaptive chromosomal mutations, but so far not with acquisition of specific resistance genes. We previously isolated Staphylococcus/Mammaliicoccus sciuri strain TS92, which displays high-level Dap-R but lacks reported adaptive mutations. To identify the underlying resistance mechanism, we performed transcription profiling upon daptomycin exposure of TS92, with subsequent subcloning and mutational analysis of candidate genes. In TS92, Dap-R is mediated by a novel two-gene operon (named drcAB), controlled by an adjacent two-component regulatory system (drcRS). Heterologous drc expression demonstrated drcAB to be required and sufficient to mediate Dap-R in S. aureus (including clinically relevant MRSA) and Bacillus subtilis via inactivation of the antibiotic. The drc genes and proteins show homologies to membrane-associated antimicrobial peptide (AMP) transporters of Gram-positive bacteria but are distinct from currently known systems. In TS92, drc is flanked by insertion sequences (IS) and integrated near a staphylococcal cassette chromosome (SCC) element, suggesting mobility and acquisition of the locus from another species. Consistent with this hypothesis, IS-flanked drc was identified in various bacterial backgrounds in database searches. Here we report for the first time a horizontally acquired Dap-R mechanism that appears to circulate among Gram-positive bacteria, including staphylococci and enterococci. Increasing clinical daptomycin usage increases the likelihood that drc may enter S. aureus and other pathogens, which calls for vigilant monitoring of drc spread and prudent use of the antibiotic.
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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
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>
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Project description:Adaptive anoikis resistance promotes ovarian cancer metastasis
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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:Antibiotic resistance (ARE) ABCF proteins are widespread, genome-encoded resistance factors in Gram-positive bacteria that rescue ribosomes stalled by antibiotics. In this study, we integrate genetic, proteomic, metabolomic, and biochemical approaches to reveal that ARE5 subfamily proteins, TiaA and Are5sc, leverage their resistance functions to regulate responses to lincosamides, streptogramins A, and pleuromutilins (LSaP) in Streptomyces coelicolor. While both Are5sc and TiaA are critical for the activation of actinorhodin production in response to LSaP antibiotics, they play distinct roles at the proteome level, determined by their differing resistance profiles and temporally regulated expression. This expression is transcriptionally induced by LSaP antibiotics via an attenuation mechanism and is reciprocally fine-tuned by the resistance functions of the ARE5 paralogs reflecting the specific type and concentration of the antibiotic. Are5sc modulates early adaptive responses by fine-tuning the WblC regulon across a broad range of antibiotic concentrations. In contrast, TiaA is induced later, at higher antibiotic concentrations, where it suppresses global antibiotic stress responses, specifically targeting pleuromutilins produced by higher fungi, reflecting a distinct ecological context compared to lincosamides and streptogramins, which are primarily produced by actinomycetes. Our study provides the first example of ARE ABCF proteins shaping antibiotic response at the translational level, expanding our understanding of the regulatory functions of these ubiquitous proteins.
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Project description:Antibiotic resistance (ARE) ABCF proteins are widespread, genome-encoded resistance factors in Gram-positive bacteria that rescue ribosomes stalled by antibiotics. In this study, we integrate genetic, proteomic, metabolomic, and biochemical approaches to reveal that ARE5 subfamily proteins, TiaA and Are5sc, leverage their resistance functions to regulate responses to lincosamides, streptogramins A, and pleuromutilins (LSaP) in Streptomyces coelicolor. While both Are5sc and TiaA are critical for the activation of actinorhodin production in response to LSaP antibiotics, they play distinct roles at the proteome level, determined by their differing resistance profiles and temporally regulated expression. This expression is transcriptionally induced by LSaP antibiotics via an attenuation mechanism and is reciprocally fine-tuned by the resistance functions of the ARE5 paralogs reflecting the specific type and concentration of the antibiotic. Are5sc modulates early adaptive responses by fine-tuning the WblC regulon across a broad range of antibiotic concentrations. In contrast, TiaA is induced later, at higher antibiotic concentrations, where it suppresses global antibiotic stress responses, specifically targeting pleuromutilins produced by higher fungi, reflecting a distinct ecological context compared to lincosamides and streptogramins, which are primarily produced by actinomycetes. Our study provides the first example of ARE ABCF proteins shaping antibiotic response at the translational level, expanding our understanding of the regulatory functions of these ubiquitous proteins.
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