Immobilization of quorum sensing inhibitors to develop antibacterial biomaterials

Abstract

Event Abstract Back to Event Immobilization of quorum sensing inhibitors to develop antibacterial biomaterials Aditi Taunk1, George Iskander1, Kitty Ka Kit Ho1, Mark D. Willcox2 and Naresh Kumar1 1 University of New South Wales, School of Chemistry, Australia 2 University of New South Wales, School of Optometry and Vision Science, Australia Introduction: The use of life-saving biomaterial implants and medical devices has increased tremendously over the past few years. One major complication with the long term use of biomaterials is bacterial biofilm formation. About 60-70% of hospital-acquired infections are due to implanted medical devices[1]. Treatment or removal of these infected devices is often troublesome for the patient resulting in high rates of morbidity and mortality as well as high medical cost[2],[3]. Also, rapid development of antibacterial resistance and lack of efficient strategies that can reduce the incidence of bacterial infections have made this a challenging problem to overcome. Therefore, in order to prevent infections associated with medical devices, coatings that interfere with the bacterial communication pathways known as quorum sensing (QS) instead of killing the bacteria have been developed. Materials and Methods: In this study, potent quorum sensing inhibitors (QSI) including halogenated furanones (FUs) and dihydropyrrolones (DHPs) were immobilized on surfaces. The FUs were attached via a non-specific nitrene insertion method [Fig 1], and DHPs with free carboxylic acid group were synthesized and attached covalently on amine functionalized surface via EDC/NHS coupling reaction [Fig 2]. The covalent attachment of DHPs was characterized by X-ray photoelectron spectroscopy (XPS) and contact angle measurement. Antibacterial activity of the DHP surfaces was assessed against two common pathogens, Staphylococcus aureus and Pseudomonas aeruginosa, using confocal laser scanning microscopy (CLSM). Results and Discussion: The XPS and contact angle measurements confirmed the successful attachment of brominated FUs via the nitrene insertion reaction and DHPs via EDC/NHS reaction. XPS detection of 0.17-0.74% Br from FUs and 0.17% F and 0.3% Br from 4-fluorophenyl and 4-bromophenyl DHP confirmed the efficacy of the coating strategy. All FU and DHP coated surfaces were able to significantly reduce the formation of biofilm against both S. aureus and P. aeruginosa. The activity of the coating was dependent upon the type of substituent present on the phenyl group of the DHP compound. For example, the ortho-fluorophenyl DHP (DHP-2) exhibited 79% reduction in bacterial adhesion against S. aureus and para-fluorophenyl DHP (DHP-3) exhibited 70% reduction against P. aeruginosa. The results were found to be comparable to other DHP coatings developed in previous studies. Conclusion: The furanone and DHP immobilised surfaces show high levels of inhibition of bacterial biofilm formation and may represent an effective strategy to develop new antibacterial coatings. UNSW Analytical Center for XPS, NMR data; UNSW Biomedical Imaging Facility for confocal microscopy; Australian government for the Australian Postgraduate Award (APA) scholarship