Evidence map›Paper›PMID 39746975›Full record

ArticleNature communications2025

Mutational signature analysis predicts bacterial hypermutation and multidrug resistance.

Kalen M Hall, Leonard G Williams, Richard D Smith, Erin A Kuang, Robert K Ernst, Christine M Bojanowski, William C Wimley, Lisa A Morici, Zachary F Pursell

Abstract read
PubMed Full text at PMC Publisher
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. Article
  2. Extended sequence context shapes mutational bias inProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
  5. Phage-Based Approaches to ChronicAntibiotics (Basel, Switzerland) · 2026
    Review
  6. 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

9 authors.

Kalen M HallDepartment of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA, USA.
Leonard G WilliamsDepartment of Biochemistry and Molecular Biology, School of Medicine, Tulane University, New Orleans, LA, USA.
Richard D SmithDepartment of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, MD, USA.
Erin A KuangDepartment of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA, USA.ORCID 0000-0002-7804-1000
Robert K ErnstDepartment of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, MD, USA.ORCID 0000-0001-5016-8694
Christine M BojanowskiDepartment of Medicine, School of Medicine, Tulane University, New Orleans, LA, USA.
William C WimleyDepartment of Biochemistry and Molecular Biology, School of Medicine, Tulane University, New Orleans, LA, USA.
Lisa A MoriciDepartment of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA, USA. lmorici@tulane.edu.ORCID 0000-0002-4799-4941
Zachary F PursellDepartment of Biochemistry and Molecular Biology, School of Medicine, Tulane University, New Orleans, LA, USA. zpursell@tulane.edu.ORCID 0000-0001-5871-7192

Funding

Mechanism of Resistance Avoidance in Synthetically Evolved Antibacterial PeptidesR21AI154284 · NIAID · TULANE UNIVERSITY OF LOUISIANA · PI WIMLEY, WILLIAM C · 2021 to 2022
$418k
Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) 5R21AI154284-02NIAID NIH HHS R21 AI154284Tulane University Provost's Proof of Concept FundTulane University Startup Funds
6 · The paper itself

Abstract

Bacteria of clinical importance, such as Pseudomonas aeruginosa, can become hypermutators upon loss of DNA mismatch repair (MMR) and are clinically correlated with high rates of multidrug resistance (MDR). Here, we demonstrate that hypermutated MMR-deficient P. aeruginosa has a unique mutational signature and rapidly acquires MDR upon repeated exposure to first-line or last-resort antibiotics. MDR acquisition was irrespective of drug class and instead arose through common resistance mechanisms shared between the initial and secondary drugs. Rational combinations of drugs having distinct resistance mechanisms prevented MDR acquisition in hypermutated MMR-deficient P. aeruginosa. Mutational signature analysis of P. aeruginosa across different human disease contexts identified appreciable quantities of MMR-deficient clinical isolates that were already MDR or prone to future MDR acquisition. Mutational signature analysis of patient samples is a promising diagnostic tool that may predict MDR and guide precision-based medical care.

Indexed as

Anti-Bacterial AgentsDNA Mismatch RepairDrug Resistance, Multiple, BacterialMutationPseudomonas aeruginosaBacterial ProteinsDNA Mutational AnalysisHumansMicrobial Sensitivity TestsPseudomonas InfectionsAnti-Bacterial AgentsBacterial Proteins

Identifiers

PMID39746975
PMCPMC11695600

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.