Evidence map›Paper›PMID 39824824›Full record

ArticleNature communications2025

High-throughput method characterizes hundreds of previously unknown antibiotic resistance mutations.

Matthew J Jago, Jake K Soley, Stepan Denisov, Calum J Walsh, Danna R Gifford, Benjamin P Howden, Mato Lagator

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
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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

7 authors.

Matthew J JagoDivision of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PL, UK.ORCID http://orcid.org/0009-0003-9511-2020
Jake K SoleyDivision of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PL, UK.ORCID http://orcid.org/0000-0001-7131-2560
Stepan DenisovDivision of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PL, UK.ORCID http://orcid.org/0000-0001-6465-3818
Calum J WalshDepartment of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia.
Danna R GiffordDivision of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PL, UK.ORCID http://orcid.org/0000-0002-4990-8816
Benjamin P HowdenDepartment of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia.ORCID http://orcid.org/0000-0003-0237-1473
Mato LagatorDivision of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PL, UK. mato.lagator@manchester.ac.uk.ORCID http://orcid.org/0000-0001-7847-3594

Funding

RCUK | Engineering and Physical Sciences Research Council (EPSRC) EP/S022856/1Wellcome TrustWellcome Trust (Wellcome) 216779/Z/19/Z
6 · The paper itself

Abstract

A fundamental obstacle to tackling the antimicrobial resistance crisis is identifying mutations that lead to resistance in a given genomic background and environment. We present a high-throughput technique - Quantitative Mutational Scan sequencing (QMS-seq) - that enables quantitative comparison of which genes are under antibiotic selection and captures how genetic background influences resistance evolution. We compare four E. coli strains exposed to ciprofloxacin, cycloserine, or nitrofurantoin and identify 812 resistance mutations, many in genes and regulatory regions not previously associated with resistance. We find that multi-drug and antibiotic-specific resistance are acquired through categorically different types of mutations, and that minor genotypic differences significantly influence evolutionary routes to resistance. By quantifying mutation frequency with single base pair resolution, QMS-seq informs about the underlying mechanisms of resistance and identifies mutational hotspots within genes. Our method provides a way to rapidly screen for resistance mutations while assessing the impact of multiple confounding factors.

Indexed as

Anti-Bacterial AgentsDrug Resistance, BacterialDrug Resistance, Multiple, BacterialEscherichia coliHigh-Throughput Nucleotide SequencingMutationCiprofloxacinCycloserineMicrobial Sensitivity TestsNitrofurantoinAnti-Bacterial AgentsCiprofloxacinCycloserineNitrofurantoin

Identifiers

PMID39824824
PMCPMC11742677

What OpenQuestion holds

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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.