ArticleThe Journal of antimicrobial chemotherapy2021
IS26-mediated amplification of blaOXA-1 and blaCTX-M-15 with concurrent outer membrane porin disruption associated with de novo carbapenem resistance in a recurrent bacteraemia cohort.
Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- Rising Carbapenem MICs and Clinical Dose Optimization: Bridging Resistance Surveillance and Pharmacokinetic/Pharmacodynamic Strategies.Antibiotics (Basel, Switzerland) · 2026Review
- Clinical and genomic determinants associated with emergent ceftazidime-avibactam plus aztreonam non-susceptibility in ceftazidime-avibactam resistantAntimicrobial agents and chemotherapy · 2026Article
- Cumulative cefepime exposure in cancer patients is associated with an increased risk of ertapenem non-susceptible, meropenem susceptible Enterobacterales bacteremia.Microbiology spectrum · 2026Article
- IncL plasmid-mediated dissemination of OXA-48 β-lactamase andJAC-antimicrobial resistance · 2026Article
- Emergence of carbapenem-resistantMicrobiology spectrum · 2025Article
- Chromosomal resistance mutations facilitate acquisition of multidrug-resistant plasmids inMicrobiology (Reading, England) · 2025Article
- Genomic Characterization of Multidrug-Resistant and ESBL-ProducingMicroorganisms · 2025Article
- A high-resolution genomic and phenotypic analysis of resistance evolution of anJournal of medical microbiology · 2025Article
- Comprehensive Assessment of Initial Adaptation of Extended-Spectrum β-Lactamase-Positive ST131 Escherichia coli to Carbapenem Exposure.The Journal of infectious diseases · 2025Article
- ISiScience · 2025Article
- ISMicrobiology and molecular biology reviews : MMBR · 2024Review
- Generation and maintenance of the circularized multimeric IS26-associated translocatable unit encoding multidrug resistance.Communications biology · 2024Article
- Vancomycin heteroresistance caused by unstable tandem amplifications of theAntimicrobial agents and chemotherapy · 2024Article
- Genomic Epidemiology of C2/H30Rx and C1-M27 Subclades ofAntibiotics (Basel, Switzerland) · 2024Article
- Heteroresistance to piperacillin/tazobactam inJAC-antimicrobial resistance · 2024Article
- Diverse Role ofAntibiotics (Basel, Switzerland) · 2024Article
- Prevalence and characterization of antimicrobial-resistantFrontiers in veterinary science · 2024Article
- Nanopore sequencing elucidatesAccess microbiology · 2024Article
- Temporal dynamics of genetically heterogeneous extended-spectrum cephalosporin-resistantmSphere · 2023Article
- Short- and Long-Read Sequencing Reveals the Presence and Evolution of an IncF Plasmid HarboringMicrobiology spectrum · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundApproximately half of clinical carbapenem-resistant Enterobacterales (CRE) isolates lack carbapenem-hydrolysing enzymes and develop carbapenem resistance through alternative mechanisms.
objectivesTo elucidate development of carbapenem resistance mechanisms from clonal, recurrent ESBL-positive Enterobacterales (ESBL-E) bacteraemia isolates in a vulnerable patient population.
methodsThis study investigated a cohort of ESBL-E bacteraemia cases in Houston, TX, USA. Oxford Nanopore Technologies long-read and Illumina short-read sequencing data were used for comparative genomic analysis. Serial passaging experiments were performed on a set of clinical ST131 Escherichia coli isolates to recapitulate in vivo observations. Quantitative PCR (qPCR) and qRT-PCR were used to determine copy number and transcript levels of β-lactamase genes, respectively.
resultsNon-carbapenemase-producing CRE (non-CP-CRE) clinical isolates emerged from an ESBL-E background through a concurrence of primarily IS26-mediated amplifications of blaOXA-1 and blaCTX-M-1 group genes coupled with porin inactivation. The discrete, modular translocatable units (TUs) that carried and amplified β-lactamase genes mobilized intracellularly from a chromosomal, IS26-bound transposon and inserted within porin genes, thereby increasing β-lactamase gene copy number and inactivating porins concurrently. The carbapenem resistance phenotype and TU-mediated β-lactamase gene amplification were recapitulated by passaging a clinical ESBL-E isolate in the presence of ertapenem. Clinical non-CP-CRE isolates had stable carbapenem resistance phenotypes in the absence of ertapenem exposure.
conclusionsThese data demonstrate IS26-mediated mechanisms underlying β-lactamase gene amplification with concurrent outer membrane porin disruption driving emergence of clinical non-CP-CRE. Furthermore, these amplifications were stable in the absence of antimicrobial pressure. Long-read sequencing can be utilized to identify unique mobile genetic element mechanisms that drive antimicrobial resistance.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.