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H Zhu, SJ Thuruthyil, S Rice, S Kjelleberg, N Kumar, RW Read, P Erickson, MD P Willcox; Inhibition of Pseudomonas aeruginosa Virulence Factors by Furanones . Invest. Ophthalmol. Vis. Sci. 2002;43(13):943.
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Purpose: Pseudomonas aeruginosa is the most common bacterial pathogen linked to contact lens-associated corneal infection. Following the initial colonization, the organism produces a numbers of virulence factors that are controlled by a group of bacterial quorum-sensing signal molecules. In the present study, the ability of halogenated furanones, a class of secondary metabolites produced by an Australian subtidal red alga, to inhibit bacterial colonization and the expression of several pathogenic traits of P. aeruginosa, at concentrations do not affect the rate of growth of this microorganism, was investigated. Methods: Bacterial colonization was measured by soaking a contact lens in a furanone solution (20 µg/cm2) overnight and then incubating the lens with P. aeruginosa 6294 cells (104 CFU/ml) suspended in an artificial tear fluid for 5 h or 24 h. The ability of furanone to inhibit protease production in P. aeruginosa broth culture was examined by using zymography and enzyme activity assay after culturing P. aeruginosa 6294 in the presence of the furanone (50 µg/ml). For testing the effects of furanones on invasion and cytotoxicity of P. aeruginosa, test strains were either pre-cultured in the presence of the furanone or co-incubated with human corneal epithelial (HCE) cells in the presence or absence of furanones. The invasiveness of P. aeruginosa 6294 and the cytotoxicity of P. aeruginosa 6206 were then determined. Results: The colonization of P. aeruginosa was reduced up to 68% and 46% on furanone-soaked lenses compared to the untreated lenses at 5-h and 24-h time points respectively. Furanone addition inhibited 70% of elastase production when compared to the control cultures. After pre-growth of either invasive or cytotoxic strain of P. aeruginosa in the presence of furanone, the invasion/cytotoxicity abilities of the test strains in HCE cells were reduced by up to 45% when compared to the untreated controls. When co-incubated with HCE cells in the presence of furanone, the furanone inhibited bacterial invasion and cytotoxicity by up to 47% and 20% respectively. Conclusion: The findings indicate that furanones have inhibitory effects on bacterial colonization, protease production, invasion and cytotoxicity. Furanones appear to be operating by inhibiting the quorum-sensing systems, and may have potential uses as therapeutic enhancements for P. aeruginosa infection.
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