Frequency of quorum-sensing mutations in Pseudomonas aeruginosa strains isolated from different environments

Abstract

<i>Pseudomonas aeruginosa</i> uses quorum sensing (QS) to coordinate the expression of multiple genes necessary for establishing and maintaining infection. It has previously been shown that <i>lasR</i> QS mutations frequently arise in cystic fibrosis (CF) lung infections, however, there has been far less emphasis on determining whether other QS system mutations arise during infection or in other environments. To test this, we utilized 852 publicly available sequenced <i>P. aeruginosa</i> genomes from the <i>Pseudomonas</i> International Consortium Database (IPCD) to study <i>P. aeruginosa</i> QS mutational signatures. 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. We also worked with a small collection of isolates <i>in vitro</i> to determine the impact of <i>lasR</i> and <i>pqs</i> mutations on isolate phenotypes. We found that <i>lasR</i> mutations are common across all environments and are not specific to infection nor a particular infection type. We also found that the <i>pqs</i> system proteins PqsA, PqsH, PqsL and MexT, a protein of increasing importance to the QS field, are highly variable. Conversely, RsaL, a negative transcriptional regulator of the <i>las</i> system, was found to be highly conserved, suggesting selective pressure to repress <i>las</i> system activity. Overall, our findings suggest that QS mutations in <i>P. aeruginosa</i> are common and not limited to the <i>las</i> system; however, LasR is unique in the frequency of putative loss-of-function mutations.