Polymer based inhibition of quorum sensing in Gram negative bacteria

Background: Bacterial quorum sensing (QS) is involved in several pathogenic bacterial processes, such as production of tissue-destroying enzymes, pyocyanin, and rhamnolipids, and biofilm formation. QS -mediated infectious diseases caused by bacteria make QS an important target for the development of materials with a novel antibacterial mode of action. Aim: To evaluate the anti- QS ability of the polymer HB-PINPAM-HL, a hyperbranched poly(NIPAM) polymer with chain ends uniquely functionalised with homoserine lactone (HL), on two Gram-negative bacteria Chromobacterium violaceum CV026 and Pseudomonas aeruginosa PAO1. Method: The polymer HB-PNIPAM-HL was first assessed for inhibition of QS in the model organism Chromobacterium violaceum CV026, and then in the pathogen Pseudomonas aeruginosa PAO1 indirectly by measuring different virulence factors (VFs). Then, the differential gene expression of bacterial genes involved in QS and VFs pathways regulated by QS systems was directly assessed following treatment with HB-PNIPAM-HL and HBPNIPAM-succ, an intermediate polymer formed during the process of HB-PNIPAM-HL production. Further analyses of the effects of the polymers on human cells were performed, which included a cytotoxicity assay and a wound healing assay (migration assay). Subsequently, the anti-QS actions of the two polymers were tested in early (2h) and late (24h) P.aeruginosa infections in a tissue-based wound infection model. Conclusion: HB- PNIPAM-HL and HB-PNIPAM -succ show promising anti-QS properties by reducing the virulence and pathogenicity of P.aeruginosa. These polymers could be an alternative to conventional antibiotics and promising non-antibiotic therapy for wound infections.