The PqsE-RhlR interaction drives virulence phenotypes in P. aeruginosa. Through mutagenesis of the PqsE active site and crystallography, we know that perturbations in the active site can disrupt this interaction, and potentially inhibit virulence. We are interested in developing active site-targeting molecules that allosterically inhibit the PqsE-RhlR interaction, as well as molecules that target the protein-protein interaction interface.

The PqsE-RhlR interaction has been confirmed as a biologically relevant protein-protein interaction in P. aeruginosa. In addition to this important interaction, we determined the PqsE-protein interaction network in the PA14 P. aeruginosa strain. Furthermore, we determined which interactions with PqsE are dependent or independent of intact PqsE catalytic function. We are now interested in validating these additional interactions and determining their potential roles in P. aeruginosa quorum sensing.

PqsE is part of an operon dedicated to the biosynthesis of signaling molecules called quinolones, including the Pseudomonas Quinolone Signal (PQS). However, the deletion of pqsE has no effect on the amount of PQS produced by P. aeruginosa, suggesting that the catalytic function of PqsE in this pathway is redundant. The question still remains: what reactions are catalyzed by PqsE in P. aeruginosa? We seek to determine the range of small molecule substrates and products of PqsE catalytic activity and whether this catalytic role plays any part in decision making by P. aeruginosa.