Genome-wide evolutionary selection pressures acting on Pseudomonas aeruginosa residing in different environments

Abstract Pseudomonas aeruginosa is an opportunistic pathogen, commonly associated with the airways of people with cystic fibrosis (CF) and in the wider environment too. In this work, we interrogate the International Pseudomonas Consortium Database (IPCD) to ask the question of whether CF-associated isolates display different patterns of evolutionary selection compared with environmental isolates. We do this by analyzing dN/dS for each open reading frame (ORF) in the CF-associated and environmental IPCD isolates. Most ORFs displayed a pronounced signature of negative selection (i.e., the ORFs were strongly conserved). However, 373 ORFs displayed non-negative selection, and of these, 206 manifested differential signatures of selection in the CF-derived and environmental isolates. Functional analysis of the ORFs under selection pressure in the CF airways revealed a statistically significant enrichment of enzymes catalyzing reactions at metabolic branchpoints. More fine-grained analyses revealed niche-specific selection pressures in individual domains and protein surfaces. Finally, we show that gene loss in the psl biosynthetic gene cluster correlates with the presence of loss-of-function mutations in the mucoidy regulator, mucA. We speculate that elevated alginate production due to these mucA mutations compensates for the loss of Psl production in these isolates.