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Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients

Author

Listed:
  • Julio Diaz Caballero

    (Department of Biology)

  • Rachel M. Wheatley

    (Department of Biology)

  • Natalia Kapel

    (Department of Biology)

  • Carla López-Causapé

    (Hospital Universitari Son Espases, Instituto de Investigación Sanitaria Illes Balears (IdISBa))

  • Thomas Van der Schalk

    (University of Antwerp)

  • Angus Quinn

    (Department of Biology)

  • Liam P. Shaw

    (Department of Biology)

  • Lois Ogunlana

    (Department of Biology)

  • Claudia Recanatini

    (University Medical Center Utrecht, Utrecht University)

  • Basil Britto Xavier

    (University of Antwerp)

  • Leen Timbermont

    (University of Antwerp)

  • Jan Kluytmans

    (University Medical Center Utrecht, Utrecht University)

  • Alexey Ruzin

    (BioPharmaceuticals R&D, AstraZeneca)

  • Mark Esser

    (BioPharmaceuticals R&D, AstraZeneca)

  • Surbhi Malhotra-Kumar

    (University of Antwerp)

  • Antonio Oliver

    (Hospital Universitari Son Espases, Instituto de Investigación Sanitaria Illes Balears (IdISBa))

  • R. Craig MacLean

    (Department of Biology)

Abstract

Antibiotic resistance poses a global health threat, but the within-host drivers of resistance remain poorly understood. Pathogen populations are often assumed to be clonal within hosts, and resistance is thought to emerge due to selection for de novo variants. Here we show that mixed strain populations are common in the opportunistic pathogen P. aeruginosa. Crucially, resistance evolves rapidly in patients colonized by multiple strains through selection for pre-existing resistant strains. In contrast, resistance evolves sporadically in patients colonized by single strains due to selection for novel resistance mutations. However, strong trade-offs between resistance and growth rate occur in mixed strain populations, suggesting that within-host diversity can also drive the loss of resistance in the absence of antibiotic treatment. In summary, we show that the within-host diversity of pathogen populations plays a key role in shaping the emergence of resistance in response to treatment.

Suggested Citation

  • Julio Diaz Caballero & Rachel M. Wheatley & Natalia Kapel & Carla López-Causapé & Thomas Van der Schalk & Angus Quinn & Liam P. Shaw & Lois Ogunlana & Claudia Recanatini & Basil Britto Xavier & Leen T, 2023. "Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39416-2
    DOI: 10.1038/s41467-023-39416-2
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    References listed on IDEAS

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