Evolution of habitat-dependent antibiotic resistance in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a human opportunistic pathogen which usually causes difficult-to-treat infections due to its low intrinsic antibiotic susceptibility and outstanding capacity of becoming resistant to antibiotics. Even more, it has a remarkable metabolic versatility, hence being able to grow in different habitats, from natural niches to different and changing in-patient environments. The study of the environmental conditions that shape genetic and phenotypic changes of P. aeruginosa towards antibiotic resistance supposes an experimental novelty, since evolution experiments are frequently performed in a well-defined antibiotic and in regular laboratory growing media. Therefore, in this work we address the extent to which the nutrients availability may constrain the evolution of antibiotic resistance. We determined that the genetic trajectories towards resistance to tobramycin, ceftazidime and ceftazidime/avibactam are different when evolving in laboratory rich medium, urine or synthetic sputum. Further, our genetic analysis showed a clear impact of each analysed environment on both fitness and resistance level associated with particular resistance mutations. This indicates that the phenotype associated with specific resistance mutations is variable and dependent on the bacterial metabolic state in each particular habitat. Our results support that the design of evolution-based strategies to tackle P. aeruginosa infections should be based on robust patterns of evolution identified within each particular type of infection and body location.