RhlR Quorum Sensing and Social Dynamics in Cystic Fibrosis-Adapted Isolates of Pseudomonas aeruginosa

Abstract

The opportunistic pathogen Pseudomonas aeruginosa is a major cause of airway infection in cystic fibrosis (CF) patients. P. aeruginosa employs several hierarchically arranged and interconnected quorum sensing (QS) regulatory circuits to produce a battery of virulence factors such as elastase, phenazines, and rhamnolipids. The QS transcription factor LasR sits atop this hierarchy, and activates the transcription of dozens of genes, including that encoding the QS regulator RhlR. Paradoxically, deleterious lasR mutations are frequently observed in isolates from CF patients with chronic P. aeruginosa infections. In contrast, mutations in rhlR are rare. We have recently shown that in CF isolates, the QS circuitry is often rewired such that RhlR acts in a LasR-independent manner. This dissertation explores how QS activity and social dynamics may differ in a rewired background through comprehensive analysis of P. aeruginosa E90, a LasR-null, RhlR-active chronic infection isolate.