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

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 Timbermont, Jan Kluytmans, Alexey Ruzin, Mark Esser, Surbhi Malhotra-Kumar, Antonio Oliver and R. Craig MacLean ()
Additional contact information
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

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-39416-2

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