Evidence map›Paper›PMID 42102167›Full record

ArticleThe ISME journal2026

Eco-evolutionary responses to plasmid-dependent phage constrain the spread of multidrug-resistance plasmids.

Daniel Cazares, Eliza Rayner, Adrian Cazares, Wendy Figueroa, David Goulding, Samuel T E Greenrod, Adam J Mulkern, Michelle Y Y Yin, Tao He, Nick Thomson and 2 more

Abstract read
In one paragraph

Article in The ISME journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Daniel CazaresDepartment of Biology, University of Oxford, Life and Mind Building, South Parks Road, Oxford, Oxfordshire OX1 3EL, United Kingdom.ORCID 0000-0002-6667-3780
Eliza RaynerDepartment of Biology, University of Oxford, Life and Mind Building, South Parks Road, Oxford, Oxfordshire OX1 3EL, United Kingdom.
Adrian CazaresParasites and Microbes Programme, Wellcome Sanger Institute, Hinxton CB10 1SA, United Kingdom.ORCID 0000-0001-6242-4405
Wendy FigueroaParasites and Microbes Programme, Wellcome Sanger Institute, Hinxton CB10 1SA, United Kingdom.ORCID 0000-0003-0882-5106
David GouldingParasites and Microbes Programme, Wellcome Sanger Institute, Hinxton CB10 1SA, United Kingdom.
Samuel T E GreenrodDepartment of Biology, University of Oxford, Life and Mind Building, South Parks Road, Oxford, Oxfordshire OX1 3EL, United Kingdom.ORCID 0000-0003-4748-6792
Adam J MulkernDepartment of Biology, University of Oxford, Life and Mind Building, South Parks Road, Oxford, Oxfordshire OX1 3EL, United Kingdom.ORCID 0000-0002-5246-6617
Michelle Y Y YinDepartment of Biology, University of Oxford, Life and Mind Building, South Parks Road, Oxford, Oxfordshire OX1 3EL, United Kingdom.ORCID 0000-0002-4694-6673
Tao HeJiangsu Academy of Agricultural Sciences, Nanjing 210040, China.
Nick ThomsonParasites and Microbes Programme, Wellcome Sanger Institute, Hinxton CB10 1SA, United Kingdom.ORCID 0000-0002-4432-8505
Michael A BrockhurstDivision of Evolution, Infection and Genomics, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9NT, United Kingdom.ORCID 0000-0003-0362-820X
R Craig MacLeanDepartment of Biology, University of Oxford, Life and Mind Building, South Parks Road, Oxford, Oxfordshire OX1 3EL, United Kingdom.ORCID 0000-0002-7941-813X

Funding

Biotechnology and Biological Sciences Research Council BB/T008784/1JPIAMR-Joint Programming Initiative on Antimicrobial ResistanceUKRI MR/W031361/1UKRI Frontiers EP/Y031067/1
6 · The paper itself

Abstract

Phage therapy offers an alternative to antibiotics for treating multidrug-resistant infections. Plasmid-dependent phages (PDPs) are promising therapeutics as they can kill targeted pathogens and prevent the spread of plasmid-encoded antibiotic resistance genes. However, the evolutionary trajectories of multidrug-resistance (MDR) plasmids under the selective pressure of PDPs remain poorly understood, particularly in eco-evolutionary contexts that remain permissive to plasmid conjugation. We experimentally evolved populations of Escherichia coli carrying the MDR plasmid RP4 in the presence of the plasmid-dependent phage PRD1 under conditions where the benefits of conjugation were either strong or weak. When opportunities for conjugation were rare, PRD1 only transiently suppressed the conjugative plasmid population due to the rapid evolution of phage-resistant plasmids lacking conjugative ability. Increasing ecological opportunities for conjugation enhanced plasmid suppression and delayed the evolution of phage-resistant plasmids. PRD1 resistance was associated with plasmid loss and reduced conjugative ability, though this trade-off was complex because resistance mutations caused heterogeneous effects on pilus production and conjugation. Mutations and insertion sequence (IS)-mediated inactivation in conjugation genes generated a spectrum of resistance phenotypes, from partial (trbB, trbL) to complete (virB4/trbE) resistance. Bioinformatic analysis of publicly available IncP plasmids revealed frequent truncations of the VirB4/TrbE protein, suggesting that plasmid-dependent phages may represent an important selective pressure shaping plasmid evolution in natural populations. Our results demonstrate an evolutionary trade-off between conjugative ability and phage resistance that plasmids cannot easily circumvent. Targeting multidrug-resistance plasmids with PDPs is likely to drive loss of conjugation, limiting the transfer of antibiotic resistance genes in microbial communities.

Indexed as

Bacteriophage PRD1Drug Resistance, Multiple, BacterialEscherichia coliEvolution, MolecularPlasmidsConjugation, Geneticconjugationconjugative pilimultidrug resistancephage resistancephage therapyplasmidplasmid-dependent phageplasmid evolution

Identifiers

PMID42102167
PMCPMC13222520

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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.