Diaz Caballero, JulioWheatley, Rachel MKapel, NataliaLópez-Causapé, CarlaVan der Schalk, ThomasQuinn, AngusShaw, Liam POgunlana, LoisRecanatini, ClaudiaXavier, Basil BrittoTimbermont, LeenKluytmans, JanRuzin, AlexeyEsser, MarkMalhotra-Kumar, SurbhiOliver, AntonioMacLean, R Craig2024-10-092024-10-092023-07-12Diaz 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.https://hdl.handle.net/20.500.13003/19376https://hdl.handle.net/20.500.12105/23720Antibiotic 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.enghttp://creativecommons.org/licenses/by/4.0/HumansPatientsDrug Resistance, Microbialresearch articleAtribución 4.0 Internacional37438338141408310.1038/s41467-023-39416-22041-1723Nature communicationsopen accessHumanosPacientesFarmacorresistencia Microbiana2-s2.0-851645412841029450400011L2024379071