Nutrient Adaptation in Pseudomonas aeruginosa

Phenotypic and whole genome sequencing analysis of Pseudomonas aeruginosa isolates from the respiratory tract of patients with cystic fibrosis have revealed common adaptions under selection in vivo. However, adaptation of bacterial populations is influenced by a number of factors including the nutrient environment, immune system, and microbiome, rendering it difficult to identify specific forces responsible for the selection of beneficial mutations. Here, we have characterized how populations of P. aeruginosa evolve in response to the abundant nutrients within the cystic fibrosis respiratory environment alone by propagating five independent lineages in minimal media mimicking the nutrients of the cystic fibrosis lung, as well as five lineages with biofilm selection to examine the effect of biofilm lifestyle on adaptation. After twelve days, WGS revealed that all planktonic populations acquired mutations in genes known to be frequently mutated during cystic fibrosis infection: morA, encoding a regulator of biofilm formation and lasR, encoding a quorum sensing system responsible for the expression of virulence factors. The parallel evolution of mutations within these two loci suggest that they produce pleiotropic fitness advantages including adaptation to the abundant nutrients within the cystic fibrosis respiratory environment. Meanwhile, biofilm populations acquired mutations to lasR and cyclic-di-GMP regulators, but selected mutations to roeA and the Wsp pathway rather than morA. These adaptations reflect that nutrient adaptation alone is sufficient to drive selection of mutants with concerning clinical phenotypes including increased biofilm and altered quorum sensing.