WS21.1 The genetic basis of Pseudomonas aeruginosa pathoadaptation to the airways of cystic fibrosis patients

Abstract

Objectives: Advances in genome sequencing have made it feasible to sequence multiple genomes of the same lineage of bacterial pathogens as they evolve in their human hosts. Nonetheless, only little is known about how evolution processes compare between genotypic different lineages of the same pathogenic species when they evolve within their human hosts. Methods: Here, we analyze the genomes of 474 isolates of P. aeruginosa sampled from 34 young Danish CF patients. Our phylogenetic analysis reveals the patients to be infected by 53 different clone types of P. aeruginosa, and for 36 of the clone types we sequenced multiple longitudinal isolates, enabling us to decipher the within-host evolutionary history of each of these lineages. Results: We found the 36 lineages to exhibit mutational convergence in 56 pathoadaptive genes (genes mutated in >5 clone types), in which the host environment imposed a selection for mutations. The pathoadaptive genes were related to motility, antibiotic resistance, remodeling of regulatory networks, biofilm formation, and extracellular virulence factors. Furthermore, our results show that mutation of downstream transcriptional regulators was contingent upon the mutation of upstream regulators in the same regulatory network. Conclusion: In conclusion, we have identified adaptive trajectories generic to P. aeruginosa in the CF environment, and elucidated how early mutations predict later evolutionary events. Knowledge of pathoadaptive mutations and evolutionary contingency may help prediction of bacterial persistence and development of future therapeutic targets against the infection.