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Synthetic Ellagic Acid Glycosides Inhibit Early Stage Adhesion of Streptococcus agalactiae Biofilms as Observed by Scanning Electron Microscopy.

ABSTRACT: Ellagic acid derivatives possess antimicrobial and antibiofilm properties across a wide-range of microbial pathogens. Due to their poor solubility and ambident reactivity it is challenging to synthesize, purify, and characterize the activity of ellagic acid glycosides. In this study, we have synthesized three ellagic acid glycoconjugates and evaluated their antimicrobial and antibiofilm activity in Streptococcus agalactiae (Group B Streptococcus, GBS). Their significant impacts on biofilm formation were examined via SEM to reveal early-stage inhibition of cellular adhesion. Additionally, the synthetic glycosides were evaluated against five of the six ESKAPE pathogens and two fungal pathogens. These studies reveal that the ellagic acid glycosides possess inhibitory effects on the growth of gram-negative pathogens.

SUBMITTER: Chambers SA

PROVIDER: S-EPMC7442748 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Synthetic Ellagic Acid Glycosides Inhibit Early Stage Adhesion of Streptococcus agalactiae Biofilms as Observed by Scanning Electron Microscopy.

Chambers Schuyler A SA Gaddy Jennifer A JA Townsend Steven D SD

Chemistry (Weinheim an der Bergstrasse, Germany) 20200421 44

Ellagic acid derivatives possess antimicrobial and antibiofilm properties across a wide-range of microbial pathogens. Due to their poor solubility and ambident reactivity it is challenging to synthesize, purify, and characterize the activity of ellagic acid glycosides. In this study, we have synthesized three ellagic acid glycoconjugates and evaluated their antimicrobial and antibiofilm activity in Streptococcus agalactiae (Group B Streptococcus, GBS). Their significant impacts on biofilm format ...[more]

PMID: 32084298

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Project description:The interaction of Porphyromonas gingivalis with commensal streptococci promotes P. gingivalis colonization of the oral cavity. We previously showed that a synthetic peptide (BAR) derived from Streptococcus gordonii potently inhibited the formation of P. gingivalis/S. gordonii biofilms (IC50 =1.3 µM) and reduced P. gingivalis virulence in a mouse model of periodontitis. Thus, BAR represents a novel therapeutic to control periodontitis by limiting P. gingivalis colonization of the oral cavity. Here, we sought to develop drug-delivery vehicles for potential use in the oral cavity that comprise BAR-modified poly(lactic-co-glycolic)acid (PLGA) nanoparticles (NPs).PLGA-NPs were initially modified with palmitylated avidin and subsequently conjugated with biotinylated BAR. The extent of BAR modification was quantified using a fluorescent-labeled peptide. Inhibition of P. gingivalis adherence to S. gordonii by BAR-modified NPs was compared with free peptide using a two-species biofilm model.BAR-modified NPs exhibited an average size of 99±29 nm and a more positive surface charge than unmodified NPs (zeta potentials of -7 mV and -25 mV, respectively). Binding saturation occurred when 37 nmol BAR/mg of avidin-NPs was used, which resulted in a payload of 7.42 nmol BAR/mg NPs. BAR-modified NPs bound to P. gingivalis in a dose-dependent manner and more potently inhibited P. gingivalis/S. gordonii adherence and biofilm formation relative to an equimolar amount of free peptide (IC50 of 0.2 µM versus 1.3 µM). BAR-modified NPs also disrupted the preformed P. gingivalis/S. gordonii biofilms more effectively than free peptide. Finally, we demonstrate that BAR-modified NPs promoted multivalent association with P. gingivalis, providing an explanation for the increased effectiveness of NPs.These results indicate that BAR-modified NPs deliver a higher local dose of peptide and may represent a more effective therapeutic approach to limit P. gingivalis colonization of the oral cavity compared to treatment with formulations of free peptide.

Dataset Information

Synthetic Ellagic Acid Glycosides Inhibit Early Stage Adhesion of Streptococcus agalactiae Biofilms as Observed by Scanning Electron Microscopy.

Publications

Synthetic Ellagic Acid Glycosides Inhibit Early Stage Adhesion of Streptococcus agalactiae Biofilms as Observed by Scanning Electron Microscopy.

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