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
N1 - Funding Information:
This research was supported by Wellcome Trust Grant (106918/Z/15/Z) and the Innovative Medicines Initiative Joint Undertaking under COMBACTE-MAGNET (Combatting Bacterial Resistance in Europe-Molecules against Gram-negative Infections, grant agreement no. 115737) and COMBACTE-NET (Combatting Bacterial Resistance in Europe-Networks, grant agreement no. 115523), resources of which are composed of financial contribution from the European Union’s Seventh Framework Program (FP7/2007-2013) and EFPIA companies’ in kind contribution. We thank the Oxford Genomics Center (funded by Wellcome Trust Grant 203141/Z/16/Z) for the generation and initial processing of Illumina sequence data. Figures within this publication were created with BioRender.com (Figs. , , and ). Figure was created using mapchart.net (CC BY-SA 4.0 licence).
Publisher Copyright:
© 2023, The Author(s).
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.
UR - http://www.scopus.com/inward/record.url?scp=85164541284&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-39416-2
DO - 10.1038/s41467-023-39416-2
M3 - Article
C2 - 37438338
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4083
ER -