Metabolomic, biochemical and genetic exploration of antimicrobial properties of Pseudomonas aeruginosa supernatants

P. aeruginosa is an opportunistic human pathogen, responsible for acute and chronic infections in immunocompromised patients. During a co-evolution experiment with S. aureus, we previously identified a mutant in the Wsp surface sensing system of P. aeruginosa. The wspF mutant displayed killing activity against S. aureus in its supernatants. Metabolomic, biochemical and genetic approaches, allowed me to identify four classes of compounds, which were necessary for S. aureus killing. Based on this, I elaborated a synthetic cocktail composed of rhamnolipids, siderophores, alkyl-n-quinolines and lysozyme, demonstrating potent killing activity against broad range of bacterial species. The killing activity was partially under the control of the GacS/GacA signalling system. Using high-resolution nanoscopy, I further showed that rhamnolipids, secreted by the wspF mutant, form micelles, which transport pyochelin into S. aureus cells. These micelles also enhanced the efficacy of lincosamide antibiotics. Altogether, my work demonstrates a novel link between surface sensing, niche colonization and interspecies competition, highlighting the extraordinary competitiveness of P. aeruginosa