Evidence map›Paper›PMID 27067320›Full record

ArticleAntimicrobial agents and chemotherapy2016

Nested Russian Doll-Like Genetic Mobility Drives Rapid Dissemination of the Carbapenem Resistance Gene blaKPC.

Anna E Sheppard, Nicole Stoesser, Daniel J Wilson, Robert Sebra, Andrew Kasarskis, Luke W Anson, Adam Giess, Louise J Pankhurst, Alison Vaughan, Christopher J Grim and 8 more

Abstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 196 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
196citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

196 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Antimicrobial agents and chemotherapy · 2026
    Article
  10. Variable chlorhexidine MICs acrossAntimicrobial agents and chemotherapy · 2026
    Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Antibiotic Resistance inAntibiotics (Basel, Switzerland) · 2026
    Review
  17. TnCurrent research in microbial sciences · 2026
    Article
  18. Review
  19. Review
  20. Article

136 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Anna E SheppardModernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom anna.sheppard@ndm.ox.ac.uk ajm5b@virginia.edu.
Nicole StoesserModernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom.ORCID 0000-0002-4508-7969
Daniel J WilsonModernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom.
Robert SebraIcahn Institute and Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, New York, USA.
Andrew KasarskisIcahn Institute and Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, New York, USA.
Luke W AnsonModernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom.
Adam GiessModernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom.
Louise J PankhurstModernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom.
Alison VaughanModernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom.
Christopher J GrimFood and Drug Administration, Laurel, Maryland, USA.
Heather L CoxDivision of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.
Anthony J YehDivision of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.
Modernising Medical Microbiology (MMM) Informatics Group
Costi D SifriDivision of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA Office of Hospital Epidemiology, University of Virginia Health System, Charlottesville, Virginia, USA.
A Sarah WalkerModernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom.
Tim E PetoModernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom.
Derrick W CrookModernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom Public Health England, Microbiology Services, London, United Kingdom.
Amy J MathersDivision of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA Clinical Microbiology, Department of Pathology, University of Virginia Health System, Charlottesville, Virginia, USA anna.sheppard@ndm.ox.ac.uk ajm5b@virginia.edu.

Funding

Department of HealthWellcome Trust
6 · The paper itself

Abstract

The recent widespread emergence of carbapenem resistance in Enterobacteriaceae is a major public health concern, as carbapenems are a therapy of last resort against this family of common bacterial pathogens. Resistance genes can mobilize via various mechanisms, including conjugation and transposition; however, the importance of this mobility in short-term evolution, such as within nosocomial outbreaks, is unknown. Using a combination of short- and long-read whole-genome sequencing of 281 blaKPC-positive Enterobacteriaceae isolates from a single hospital over 5 years, we demonstrate rapid dissemination of this carbapenem resistance gene to multiple species, strains, and plasmids. Mobility of blaKPC occurs at multiple nested genetic levels, with transmission of blaKPC strains between individuals, frequent transfer of blaKPC plasmids between strains/species, and frequent transposition of blaKPC transposon Tn4401 between plasmids. We also identify a common insertion site for Tn4401 within various Tn2-like elements, suggesting that homologous recombination between Tn2-like elements has enhanced the spread of Tn4401 between different plasmid vectors. Furthermore, while short-read sequencing has known limitations for plasmid assembly, various studies have attempted to overcome this by the use of reference-based methods. We also demonstrate that, as a consequence of the genetic mobility observed in this study, plasmid structures can be extremely dynamic, and therefore these reference-based methods, as well as traditional partial typing methods, can produce very misleading conclusions. Overall, our findings demonstrate that nonclonal resistance gene dissemination can be extremely rapid, presenting significant challenges for public health surveillance and achieving effective control of antibiotic resistance.

Indexed as

Gene Transfer, HorizontalAnti-Bacterial AgentsBacterial Typing Techniquesbeta-Lactamasesbeta-Lactam ResistanceCarbapenemsConjugation, GeneticDNA Transposable ElementsEnterobacteriaceaeEnterobacteriaceae InfectionsGene ExpressionHigh-Throughput Nucleotide SequencingHomologous RecombinationHumansPhylogenyPlasmidsAnti-Bacterial Agentsbeta-LactamasesCarbapenemsDNA Transposable Elements

Identifiers

PMID27067320
PMCPMC4879409

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.