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

Here, Caballero et al. provide an in depth characterisation of patients colonized with single or mixed strains of Pseudomonas aeruginosa to demonstrate the impact of within-host diversity on the development of antibiotic resistance. 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.

Automated summary

Here, the authors extensively characterized patients colonized with different strains of Pseudomonas aeruginosa to study the impact of within-host diversity on the development of antibiotic resistance. They found that mixed strain populations are common in this pathogen, and resistance rapidly evolves through selection for pre-existing resistant strains in patients colonized with multiple strains. In contrast, resistance sporadically evolves in patients colonized with a single strain due to selection for novel resistance mutations. Furthermore, the study suggests that within-host diversity can also lead to the loss of resistance in the absence of antibiotic treatment.