Evidence map›Paper›PMID 38485998›Full record

ArticleNature communications2024

Bacteria can compensate the fitness costs of amplified resistance genes via a bypass mechanism.

Ankita Pal, Dan I Andersson

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 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
–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

36 citing papers in PubMed.

  1. Within-patient carbapenem heteroresistance inCurrent research in microbial sciences · 2026
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  19. Resistance, heteroresistance, and fitness costs drive colistin treatment failure duringProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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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

2 authors.

Ankita PalDepartment of Medical Biochemistry and Microbiology, Uppsala University, Box 582, SE-751 23, Uppsala, Sweden.
Dan I AnderssonDepartment of Medical Biochemistry and Microbiology, Uppsala University, Box 582, SE-751 23, Uppsala, Sweden. dan.andersson@imbim.uu.se.ORCID 0000-0001-6640-2174

Funding

Single Cell Analysis Core (Core C)U19AI158080 · NIAID · EMORY UNIVERSITY · PI LEVIN, BRUCE RICHARD · 2021 to 2025
$10.9M
Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation) 2018.0168NIAID NIH HHS U19 AI158080U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) 1U19AI158080-01Vetenskapsrådet (Swedish Research Council) 2021-02091
6 · The paper itself

Abstract

Antibiotic heteroresistance is a phenotype in which a susceptible bacterial population includes a small subpopulation of cells that are more resistant than the main population. Such resistance can arise by tandem amplification of DNA regions containing resistance genes that in single copy are not sufficient to confer resistance. However, tandem amplifications often carry fitness costs, manifested as reduced growth rates. Here, we investigated if and how these fitness costs can be genetically ameliorated. We evolved four clinical isolates of three bacterial species that show heteroresistance to tobramycin, gentamicin and tetracyclines at increasing antibiotic concentrations above the minimal inhibitory concentration (MIC) of the main susceptible population. This led to a rapid enrichment of resistant cells with up to an 80-fold increase in the resistance gene copy number, an increased MIC, and severely reduced growth rates. When further evolved in the presence of antibiotic, these strains acquired compensatory resistance mutations and showed a reduction in copy number while maintaining high-level resistance. A deterministic model indicated that the loss of amplified units was driven mainly by their fitness costs and that the compensatory mutations did not affect the loss rate of the gene amplifications. Our findings suggest that heteroresistance mediated by copy number changes can facilitate and precede the evolution towards stable resistance.

Indexed as

Anti-Bacterial AgentsTobramycinBacteriaDrug Resistance, BacterialGene AmplificationGentamicinsMicrobial Sensitivity TestsAnti-Bacterial AgentsGentamicinsTobramycin

Identifiers

PMID38485998
PMCPMC10940297

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Registered trials

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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.