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oai:repisalud.isciii.es:20.500.12105/237202024-11-28T23:52:08Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Diaz Caballero, Julio author Wheatley, Rachel M author Kapel, Natalia author López-Causapé, Carla author Van der Schalk, Thomas author Quinn, Angus author Shaw, Liam P author Ogunlana, Lois author Recanatini, Claudia author Xavier, Basil Britto author Timbermont, Leen author Kluytmans, Jan author Ruzin, Alexey author Esser, Mark author Malhotra-Kumar, Surbhi author Oliver, Antonio author MacLean, R Craig author 2023-07-12 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. Diaz Caballero J, Wheatley RM, Kapel N, López-Causapé C, Van der Schalk T, Quinn A, et al. Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients. Nat Commun. 2023 Jul 12;14(1):4083. 10.1038/s41467-023-39416-2 2041-1723 Nature communications https://hdl.handle.net/20.500.13003/19376 37438338 L2024379071 2-s2.0-85164541284 https://hdl.handle.net/20.500.12105/23720 1029450400011 Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients