Evidence map›Paper›PMID 38730266›Full record

ArticleNature communications2024

Three concurrent mechanisms generate gene copy number variation and transient antibiotic heteroresistance.

Hervé Nicoloff, Karin Hjort, Dan I Andersson, Helen Wang

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing 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

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

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Heteroresistance to amikacin inMicrobiology spectrum · 2026
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Heterogeneous multicopy of blaNature communications · 2026
    Article
  15. Review
  16. Review
  17. Review
  18. Nitrogen-fixing microbes gain genes in diverse types of living environments.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Article
  20. Article
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

4 authors.

Hervé NicoloffDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. herve.nicoloff@imbim.uu.se.ORCID http://orcid.org/0000-0002-4848-1371
Karin HjortDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0003-3326-8495
Dan I AnderssonDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0001-6640-2174
Helen WangDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. helen.wang@imbim.uu.se.ORCID http://orcid.org/0000-0003-4757-1583

Funding

Single Cell Analysis Core (Core C)U19AI158080 · NIAID · EMORY UNIVERSITY · PI LEVIN, BRUCE RICHARD · 2021 to 2025
$10.9M
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) 1U19AI158080-01Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation) 2018.0168NIAID NIH HHS U19 AI158080Svenska Sällskapet för Medicinsk Forskning (Swedish Society for Medical Research) S18-0174Vetenskapsrådet (Swedish Research Council) 2018-02376Vetenskapsrådet (Swedish Research Council) 2021-02091Vetenskapsrådet (Swedish Research Council) 2022-0074
6 · The paper itself

Abstract

Heteroresistance is a medically relevant phenotype where small antibiotic-resistant subpopulations coexist within predominantly susceptible bacterial populations. Heteroresistance reduces treatment efficacy across diverse bacterial species and antibiotic classes, yet its genetic and physiological mechanisms remain poorly understood. Here, we investigated a multi-resistant Klebsiella pneumoniae isolate and identified three primary drivers of gene dosage-dependent heteroresistance for several antibiotic classes: tandem amplification, increased plasmid copy number, and transposition of resistance genes onto cryptic plasmids. All three mechanisms imposed fitness costs and were genetically unstable, leading to fast reversion to susceptibility in the absence of antibiotics. We used a mouse gut colonization model to show that heteroresistance due to elevated resistance-gene dosage can result in antibiotic treatment failures. Importantly, we observed that the three mechanisms are prevalent among Escherichia coli bloodstream isolates. Our findings underscore the necessity for treatment strategies that address the complex interplay between plasmids, resistance cassettes, and transposons in bacterial populations.

Indexed as

Anti-Bacterial AgentsDNA Copy Number VariationsEscherichia coliKlebsiella pneumoniaePlasmidsAnimalsDNA Transposable ElementsDrug Resistance, Multiple, BacterialFemaleGene DosageHumansKlebsiella InfectionsMiceMicrobial Sensitivity TestsAnti-Bacterial AgentsDNA Transposable Elements

Identifiers

PMID38730266
PMCPMC11087502

What OpenQuestion holds

Textmetadata
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.