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; R Craig MacLean

doi:10.1038/s41467-023-39416-2

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, R Craig MacLean

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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.

Original language	English
Article number	4083
Number of pages	12
Journal	Nature Communications
Volume	14
DOIs	https://doi.org/10.1038/s41467-023-39416-2
Publication status	Published - 12 Jul 2023
Externally published	Yes

Bibliographical note

Keywords

Humans
Drug Resistance, Microbial/genetics
Patients

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10.1038/s41467-023-39416-2Licence: CC BY

Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients
Copyright 2023 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 2.09 MBLicence: CC BY

Cite this

Diaz Caballero, J., Wheatley, R. M., Kapel, N., López-Causapé, C., Van der Schalk, T., Quinn, A., Shaw, L. P., Ogunlana, L., Recanatini, C., Xavier, B. B., Timbermont, L., Kluytmans, J., Ruzin, A., Esser, M., Malhotra-Kumar, S., Oliver, A., & MacLean, R. C. (2023). Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients. Nature Communications, 14, Article 4083. https://doi.org/10.1038/s41467-023-39416-2

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title = "Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients",

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.",

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Diaz Caballero, J, Wheatley, RM, Kapel, N, López-Causapé, C, Van der Schalk, T, Quinn, A, Shaw, LP, Ogunlana, L, Recanatini, C, Xavier, BB, Timbermont, L, Kluytmans, J, Ruzin, A, Esser, M, Malhotra-Kumar, S, Oliver, A & MacLean, RC 2023, 'Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients', Nature Communications, vol. 14, 4083. https://doi.org/10.1038/s41467-023-39416-2

TY - JOUR

T1 - Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients

AU - Diaz Caballero, Julio

AU - Wheatley, Rachel M

AU - Kapel, Natalia

AU - López-Causapé, Carla

AU - Van der Schalk, Thomas

AU - Quinn, Angus

AU - Shaw, Liam P

AU - Ogunlana, Lois

AU - Recanatini, Claudia

AU - Xavier, Basil Britto

AU - Timbermont, Leen

AU - Kluytmans, Jan

AU - Ruzin, Alexey

AU - Esser, Mark

AU - Malhotra-Kumar, Surbhi

AU - Oliver, Antonio

AU - MacLean, R Craig

PY - 2023/7/12

Y1 - 2023/7/12

N2 - 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.

AB - 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.

KW - Humans

KW - Drug Resistance, Microbial/genetics

KW - Patients

U2 - 10.1038/s41467-023-39416-2

DO - 10.1038/s41467-023-39416-2

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C2 - 37438338

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

M1 - 4083

ER -

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

Abstract

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