Novel Antibacterial Biomaterials and Polymers Based on Quorum Sensing Inhibitors

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Embargoed until 2020-03-01
Copyright: Taunk, Aditi
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Abstract
Bacterial biofilms on life-saving implanted medical devices are a serious problem in long-term. At present, no effective strategies are available and the emergence of multi-drug resistance has highlighted the need to develop novel antibacterial coatings to combat device-related infections. One approach is to block the bacterial communication pathway or quorum sensing (QS), which is responsible for biofilm formation, by incorporating QS inhibitors (QSIs) such as dihydropyrrolones (DHPs) and furanones (FUs) on biomaterial surfaces and polymers. The endogenous biological signalling molecule nitric oxide (NO) is also a potential candidate for prevention of biomedical infections due to its antibiofilm activity. In this study, DHPs and brominated FUs were immobilized on surfaces via a non-specific nitrene-insertion method. The successful covalent attachment of compounds was confirmed by X-ray photoelectron spectroscopy. The coated surfaces showed excellent in vitro activity against Staphylococcus aureus and Pseudomonas aeruginosa. Interestingly, DHP surfaces at low concentrations (0.17–0.35 % halogen) were found to display similar levels of activity as FUs with higher surface attachment (0.41–0.74 % Br), which was possibly due to change in orientation of DHP during attachment. The influence of DHP orientation and absence of an exocyclic double bond on the biological activity was then examined by specific covalent attachment using EDC/NHS coupling. The orientation of DHP with free lactam ring exposed to bacterial medium showed higher activity compared to DHPs attached from the nitrogen of the lactam ring. In addition, DHPs lacking the exocyclic double bond were also able to reduce bacterial adhesion without killing both strains of bacteria, indicating DHPs retained their activity even in absence of the exocyclic bond. This project also focused on developing dual-action surfaces and polymers that were functionalized by DHPs via Michael-addition reaction and diazeniumdiolates (NO donors) derived from the reaction of secondary amines with NO gas. The DHP+NO surfaces demonstrated significantly higher efficacy in reducing colonization of both bacterial strains than the DHP coatings alone, while the hybrid polymer displayed excellent activity by inhibiting 95 % of P. aeruginosa biofilm at all concentrations (42–1 µM) via a non-toxic mechanism. Therefore, the coatings based on QSIs show great potential in reducing device-related infections.
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Author(s)
Taunk, Aditi
Supervisor(s)
Kumar, Naresh
Willcox, Mark DP
Black, David StC
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Publication Year
2017
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
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