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|Title:||Epigallocatechin gallate remodels overexpressed functional amyloids in Pseudomonas aeruginosa and Increases biofilm susceptibility to antibiotic treatment||Authors:||Stenvang, Marcel
Dueholm, Morten S.
Vad, Brian S.
Søndergaard, Mads T.
Meyer, Rikke Louise
Nielsen, Per Halkjær
Otzen, Daniel E.
|Issue Date:||2016||Source:||Stenvang, M., Dueholm, M. S., Vad, B. S., Seviour, T., Zeng, G., Geifman-Shochat, S., . . . Otzen, D. E. (2016). Epigallocatechin gallate remodels overexpressed functional amyloids in Pseudomonas aeruginosa and increases biofilm susceptibility to antibiotic treatment. Journal of Biological Chemistry, 291(51), 26540-26553. doi:10.1074/jbc.M116.739953||Series/Report no.:||Journal of Biological Chemistry||Abstract:||Epigallocatechin-3-gallate (EGCG) is the major polyphenol in green tea. It has antimicrobial properties and disrupts the ordered structure of amyloid fibrils involved in human disease. The antimicrobial effect of EGCG against the opportunistic pathogen Pseudomonas aeruginosa has been shown to involve disruption of quorum sensing (QS). Functional amyloid fibrils in P. aeruginosa (Fap) are able to bind and retain quorum-sensing molecules, suggesting that EGCG interferes with QS through structural remodeling of amyloid fibrils. Here we show that EGCG inhibits the ability of Fap to form fibrils; instead, EGCG stabilizes protein oligomers. Existing fibrils are remodeled by EGCG into non-amyloid aggregates. This fibril remodeling increases the binding of pyocyanin, demonstrating a mechanism by which EGCG can affect the QS function of functional amyloid. EGCG reduced the amyloid-specific fluorescent thioflavin T signal in P. aeruginosa biofilms at concentrations known to exert an antimicrobial effect. Nanoindentation studies showed that EGCG reduced the stiffness of biofilm containing Fap fibrils but not in biofilm with little Fap. In a combination treatment with EGCG and tobramycin, EGCG had a moderate effect on the minimum bactericidal eradication concentration against wild-type P. aeruginosa biofilms, whereas EGCG had a more pronounced effect when Fap was overexpressed. Our results provide a direct molecular explanation for the ability of EGCG to disrupt P. aeruginosa QS and modify its biofilm and strengthens the case for EGCG as a candidate in multidrug treatment of persistent biofilm infections.||URI:||https://hdl.handle.net/10356/89405
|ISSN:||0021-9258||DOI:||http://dx.doi.org/10.1074/jbc.M116.739953||Rights:||© 2016 The American Society for Biochemistry and Molecular Biology, Inc. This paper was published in Journal of Biological Chemistry and is made available as an electronic reprint (preprint) with permission of The American Society for Biochemistry and Molecular Biology, Inc. The published version is available at: [http://dx.doi.org/10.1074/jbc.M116.739953]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.||metadata.item.grantfulltext:||open||metadata.item.fulltext:||With Fulltext|
|Appears in Collections:||SCELSE Journal Articles|
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