Abstract
Pseudomonas aeruginosa uses quorum sensing (QS) to coordinate the expression of multiple genes necessary for establishing and maintaining infection. lasR QS mutations have been shown to frequently arise in cystic fibrosis (CF) lung infections, however, there has been far less emphasis on determining whether QS system mutations arise across other environments. To test this, we utilized 852 publicly available sequenced P. aeruginosa genomes from the Pseudomonas International Consortium Database (IPCD) to study P. aeruginosa QS mutational signatures. We found that across all isolates, LasR is the most variable protein sequence compared to other QS proteins. In order to study isolates by source, we focused on a subset of 654 isolates collected from CF, wounds, and non-infection environmental isolates, where we could clearly identify their source. Using this sub-set analysis, we found that LasR mutations are not specific to CF lungs, but are common across all environments. We then used amino acid length as a proxy for observing loss of function in LasR proteins among the strains. We found that truncated LasR proteins are more abundant in P. aeruginosa strains isolated from human infection than the environment. Overall, our findings suggest that the evolution of lasR QS mutations in P. aeruginosa are common and not limited to infection environments.
Importance Pseudomonas aeruginosa is an opportunistic pathogen which is often isolated from infection and environmental sources. P. aeruginosa uses quorum sensing (QS) to establish and adapt to infection environments. QS in P. aeruginosa is controlled by a complex hierarchical gene network in which the transcriptional regulator LasR has traditionally been thought to play a major controlling role. Despite this, lasR mutants are frequently isolated from chronic infection sites including the cystic fibrosis lung. Using an online P. aeruginosa strain database, we determined the frequency of mutation in key QS genes in multiple infection and non-infection environments and found that mutations and truncations in the lasR gene is more common than in other QS genes. Further, we found that lasR mutants are common in both infection and environmental strains. These findings further our understanding of QS in P. aeruginosa and have implications for the development of future therapies designed to inhibit QS.
Competing Interest Statement
The authors have declared no competing interest.