title: Poly(ε-lysine) dendrons as modulators of quorum sensing in Pseudomonas aeruginosa.
abstract: The opportunistic pathogen Pseudomonas aeruginosa is a significant contributor to recalcitrant multi-drug resistant infections. In a vigorous search for alternative therapeutic approaches, the communication system used by this bacterium to synchronise the expression of genes involved in pathogenicity has been identified as a potential target. Poly(ε-lysine) dendrons, composed of three branching generations, were examined herein for their anti-virulence potential and ability to disperse within P. a eruginosa biofilms. These hyperbranched macromolecules reduced attachment and biomass production under different nutrient growth conditions, and at concentrations that were not lethal to planktonic cells (0.2, 0.4 and 0.8 mg/mL). Fluorescent labelling revealed the intracellular localisation and cell-penetrating capacity of the dendron, and showed the rapid uptake and release of unexploited dendron from pre-established P. a eruginosa biofilms. Additionally, the dendron induced complete attenuation of LasA protease, a marker of quorum sensing inactivation, by preventing its accumulation in the external environment. This study thus demonstrates the anti-virulence potential of this class of macromolecules, and could represent a novel therapeutic approach for the treatment of antibiotic-resistant P. a eruginosa infections.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Lewes Road, Brighton, BN2 4GJ, UK, r.issa1@uni.brighton.ac.uk.
authors.forename: Rahaf
authors.initials: R
authors.lastname: Issa
authors.forename: Steve T
authors.initials: ST
authors.lastname: Meikle
authors.forename: Stuart
authors.initials: S
authors.lastname: James
authors.forename: Ian R
authors.initials: IR
authors.lastname: Cooper
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology; D008422:Materials Testing; D011107:Polylysine / Q000737:chemistry* / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology*; D053038:Quorum Sensing / Q000187:drug effects / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D050091:Dendrimers; D011107:Polylysine