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Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection

Author

Listed:
  • Rachel Wheatley

    (University of Oxford, Department of Zoology)

  • Julio Diaz Caballero

    (University of Oxford, Department of Zoology)

  • Natalia Kapel

    (University of Oxford, Department of Zoology)

  • Fien H. R. Winter

    (Vaccine and Infectious Disease Institute, University of Antwerp)

  • Pramod Jangir

    (University of Oxford, Department of Zoology)

  • Angus Quinn

    (University of Oxford, Department of Zoology)

  • Ester Barrio-Tofiño

    (Hospital Universitario Son Espases)

  • Carla López-Causapé

    (Hospital Universitario Son Espases)

  • Jessica Hedge

    (University of Oxford, Department of Zoology)

  • Gabriel Torrens

    (Hospital Universitario Son Espases)

  • Thomas Schalk

    (Vaccine and Infectious Disease Institute, University of Antwerp)

  • Basil Britto Xavier

    (Vaccine and Infectious Disease Institute, University of Antwerp)

  • Felipe Fernández-Cuenca

    (Universidad de Sevilla)

  • Angel Arenzana

    (Universidad de Sevilla)

  • Claudia Recanatini

    (University Medical Center Utrecht, Utrecht University)

  • Leen Timbermont

    (Vaccine and Infectious Disease Institute, University of Antwerp)

  • Frangiscos Sifakis

    (Boehringer Ingelheim Pharmaceuticals, Inc)

  • Alexey Ruzin

    (Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca)

  • Omar Ali

    (Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca
    Viela Bio)

  • Christine Lammens

    (Vaccine and Infectious Disease Institute, University of Antwerp)

  • Herman Goossens

    (Vaccine and Infectious Disease Institute, University of Antwerp)

  • Jan Kluytmans

    (University Medical Center Utrecht, Utrecht University
    Microvida Laboratory for Medical Microbiology and Department of Infection Control, Amphia Hospital)

  • Samir Kumar-Singh

    (Vaccine and Infectious Disease Institute, University of Antwerp
    University of Antwerp)

  • Antonio Oliver

    (Hospital Universitario Son Espases)

  • Surbhi Malhotra-Kumar

    (Vaccine and Infectious Disease Institute, University of Antwerp)

  • Craig MacLean

    (University of Oxford, Department of Zoology)

Abstract

It is well established that antibiotic treatment selects for resistance, but the dynamics of this process during infections are poorly understood. Here we map the responses of Pseudomonas aeruginosa to treatment in high definition during a lung infection of a single ICU patient. Host immunity and antibiotic therapy with meropenem suppressed P. aeruginosa, but a second wave of infection emerged due to the growth of oprD and wbpM meropenem resistant mutants that evolved in situ. Selection then led to a loss of resistance by decreasing the prevalence of low fitness oprD mutants, increasing the frequency of high fitness mutants lacking the MexAB-OprM efflux pump, and decreasing the copy number of a multidrug resistance plasmid. Ultimately, host immunity suppressed wbpM mutants with high meropenem resistance and fitness. Our study highlights how natural selection and host immunity interact to drive both the rapid rise, and fall, of resistance during infection.

Suggested Citation

  • Rachel Wheatley & Julio Diaz Caballero & Natalia Kapel & Fien H. R. Winter & Pramod Jangir & Angus Quinn & Ester Barrio-Tofiño & Carla López-Causapé & Jessica Hedge & Gabriel Torrens & Thomas Schalk &, 2021. "Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22814-9
    DOI: 10.1038/s41467-021-22814-9
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    Cited by:

    1. 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.
    2. Hattie Chung & Christina Merakou & Matthew M. Schaefers & Kelly B. Flett & Sarah Martini & Roger Lu & Jennifer A. Blumenthal & Shanice S. Webster & Ashley R. Cross & Roy Al Ahmar & Erin Halpin & Miche, 2022. "Rapid expansion and extinction of antibiotic resistance mutations during treatment of acute bacterial respiratory infections," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    3. Rachel M. Wheatley & Julio Diaz Caballero & Thomas E. Schalk & Fien H. R. Winter & Liam P. Shaw & Natalia Kapel & Claudia Recanatini & Leen Timbermont & Jan Kluytmans & Mark Esser & Alicia Lacoma & Cr, 2022. "Gut to lung translocation and antibiotic mediated selection shape the dynamics of Pseudomonas aeruginosa in an ICU patient," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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