title: Quorum sensing inhibitory activities of surface immobilized antibacterial dihydropyrrolones via click chemistry.
abstract: Device-related infection remains a major barrier to the use of biomaterial implants as life-saving devices. This study aims to examine the effectiveness and mechanism of action of surface attached dihydropyrrolones (DHPs), a quorum sensing (QS) inhibitor, against bacterial colonization. DHPs were covalently attached on glass surfaces via copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) click reaction. The covalent attachment of DHP surfaces was confirmed by X-ray photoelectron spectroscopy (XPS) and contact angle measurements, and the antimicrobial efficacy of the DHP coatings was assessed by confocal laser scanning microscopy (CLSM) and image analysis. The results demonstrated that covalently bound DHP compounds are effective in reducing the adhesion by up to 97% (p < 0.05) for both Pseudomonas aeruginosa and Staphylococcus aureus. Furthermore, using the green fluorescent protein (Gfp)-based reporter technology, it is demonstrated that surface attached DHPs were able to repress the expression of a lasB-gfp reporter fusion of P. aeruginosa by 72% (p < 0.001) without affecting cell viability. This demonstrates the ability of the covalently bound QS inhibitor to inhibit QS and suggests the existence of a membrane-based pathway(s) for QS inhibition. Hence, strategies based on incorporation of QS inhibitors such as DHPs represent a potential approach for prevention of device-related infections.
authors.affiliation: School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Kitty K K
authors.initials: KK
authors.lastname: Ho
authors.affiliation: School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Renxun
authors.initials: R
authors.lastname: Chen
authors.affiliation: School of Optometry and Vision Science, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Mark D P
authors.initials: MD
authors.lastname: Willcox
authors.affiliation: School of Biotechnology and Biomolecular Sciences and The Centre for Marine Bio-Innovation, University of New South Wales, Sydney, NSW 2052, Australia; The Singapore Centre on Environmental Life Sciences Engineering, School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rice
authors.affiliation: School of Optometry and Vision Science, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Nerida
authors.initials: N
authors.lastname: Cole
authors.affiliation: School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: George
authors.initials: G
authors.lastname: Iskander
authors.affiliation: School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: n.kumar@unsw.edu.au.
authors.forename: Naresh
authors.initials: N
authors.lastname: Kumar
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D057930:Click Chemistry; D018613:Microscopy, Confocal; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D053038:Quorum Sensing; D013057:Spectrum Analysis / Q000379:methods; D013211:Staphylococcus aureus / Q000187:drug effects; D013499:Surface Properties
chemical_list: D000900:Anti-Bacterial Agents; D011758:Pyrroles
keywords: Antibacterial; Dihydropyrrolone; Pseudomonas; Quorum sensing; Staphylococcus; Surface modification