A new Pseudomonas quinolone signal (PQS) binding partner: MexG

Abstract

The opportunistic pathogen <i>Pseudomonas aeruginosa</i> utilises the cell-cell signalling mechanism known as quorum sensing to regulate virulence. <i>P. aeruginosa</i> produces two quinolone-based quorum sensing signalling molecules; the <i>Pseudomonas</i> quinolone signal (PQS) and its biosynthetic precursor 2-heptyl-4(1<i>H</i>)-quinolone (HHQ). To date, only one receptor (the PqsR protein) has been identified that is capable of binding PQS and HHQ. Here, we report on the synthesis of PQS and HHQ affinity probes for chemical proteomic studies. The PQS affinity probe very effectively captured PqsR <i>in vitro</i>. In addition, we also identified an interaction between PQS and the "orphan" RND efflux pump protein, MexG. The PQS-MexG interaction was further confirmed by purifying MexG and characterizing its ability to bind PQS and HHQ <i>in vitro</i>. Our findings suggest that PQS may have multiple binding partners in the cell and provide important new tools for studying quinolone signalling in <i>P. aeruginosa</i> and other organisms.