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

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, Basil Britto Xavier, Felipe Fernández-Cuenca, Angel Arenzana, Claudia Recanatini, Leen Timbermont, Frangiscos Sifakis, Alexey Ruzin, Omar Ali, Christine Lammens, Herman Goossens, Jan Kluytmans, Samir Kumar-Singh, Antonio Oliver, Surbhi Malhotra-Kumar and Craig MacLean ()
Additional contact information
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
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
Samir Kumar-Singh: Vaccine and Infectious Disease Institute, 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

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22814-9

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DOI: 10.1038/s41467-021-22814-9

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