Social cheating in a <i>Pseudomonas aeruginosa</i> quorum-sensing variant.

Abstract

The opportunistic bacterial pathogen <i>Pseudomonas aeruginosa</i> has a layered acyl-homoserine lactone (AHL) quorum-sensing (QS) system, which controls production of a variety of extracellular metabolites and enzymes. The LasRI system activates genes including those coding for the extracellular protease elastase and for the second AHL QS system, RhlRI. Growth of <i>P. aeruginosa</i> on casein requires elastase production and LasR-mutant social cheats emerge in populations growing on casein. <i>P. aeruginosa</i> colonizes the lungs of individuals with the genetic disease cystic fibrosis (CF), and LasR mutants can be isolated from the colonized lungs; however, unlike laboratory-generated LasR mutants, many of these CF isolates have functioning RhlR-RhlI systems. We show that one such mutant can use the RhlR-RhlI system to activate expression of elastase and grow on casein. We carried out social-evolution experiments by growing this isolate on caseinate and, as with wild-type <i>P. aeruginosa</i>, elastase-negative mutants emerge as cheats, but these are not RhlR mutants; rather, they are mutants that do not produce the non-AHL <i>Pseudomonas</i> quinolone signal (PQS). Furthermore, we generated a RhlRI mutant and showed it had a fitness defect when growing together with the parent. Apparently, RhlR QS and PQS collude to support growth on caseinate in the absence of a functional LasR. Our findings provide a plausible explanation as to why <i>P. aeruginosa</i> LasR mutants, but not RhlR mutants, are common in CF lungs.