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Antimicrobial and efflux pump inhibitory activity of caffeoylquinic acids from Artemisia absinthium against gram-positive pathogenic bacteria.

ABSTRACT: BACKGROUND:Traditional antibiotics are increasingly suffering from the emergence of multidrug resistance amongst pathogenic bacteria leading to a range of novel approaches to control microbial infections being investigated as potential alternative treatments. One plausible antimicrobial alternative could be the combination of conventional antimicrobial agents/antibiotics with small molecules which block multidrug efflux systems known as efflux pump inhibitors. Bioassay-driven purification and structural determination of compounds from plant sources have yielded a number of pump inhibitors which acted against gram positive bacteria. METHODOLOGY/PRINCIPAL FINDINGS:In this study we report the identification and characterization of 4',5'-O-dicaffeoylquinic acid (4',5'-ODCQA) from Artemisia absinthium as a pump inhibitor with a potential of targeting efflux systems in a wide panel of gram-positive human pathogenic bacteria. Separation and identification of phenolic compounds (chlorogenic acid, 3',5'-ODCQA, 4',5'-ODCQA) was based on hyphenated chromatographic techniques such as liquid chromatography with post column solid-phase extraction coupled with nuclear magnetic resonance spectroscopy and mass spectroscopy. Microbial susceptibility testing and potentiation of well know pump substrates revealed at least two active compounds; chlorogenic acid with weak antimicrobial activity and 4',5'-ODCQA with pump inhibitory activity whereas 3',5'-ODCQA was ineffective. These initial findings were further validated with checkerboard, berberine accumulation efflux assays using efflux-related phenotypes and clinical isolates as well as molecular modeling methodology. CONCLUSIONS/SIGNIFICANCE:These techniques facilitated the direct analysis of the active components from plant extracts, as well as dramatically reduced the time needed to analyze the compounds, without the need for prior isolation. The calculated energetics of the docking poses supported the biological information for the inhibitory capabilities of 4',5'-ODCQA and furthermore contributed evidence that CQAs show a preferential binding to Major Facilitator Super family efflux systems, a key multidrug resistance determinant in gram-positive bacteria.

SUBMITTER: Fiamegos YC

PROVIDER: S-EPMC3070693 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Antimicrobial and efflux pump inhibitory activity of caffeoylquinic acids from Artemisia absinthium against gram-positive pathogenic bacteria.

Fiamegos Yiannis C YC Kastritis Panagiotis L PL Exarchou Vassiliki V Han Haley H Bonvin Alexandre M J J AM Vervoort Jacques J Lewis Kim K Hamblin Michael R MR Tegos George P GP

PloS one 20110404 4

<h4>Background</h4>Traditional antibiotics are increasingly suffering from the emergence of multidrug resistance amongst pathogenic bacteria leading to a range of novel approaches to control microbial infections being investigated as potential alternative treatments. One plausible antimicrobial alternative could be the combination of conventional antimicrobial agents/antibiotics with small molecules which block multidrug efflux systems known as efflux pump inhibitors. Bioassay-driven purificatio ...[more]

PMID: 21483731

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Project description:Caffeoylquinic acids are some of the chemophenetically significant specialized metabolites found in plants of the family Asteraceae Dumort., possessing a broad spectrum of biological activities. As they might be potential mitochondria-targeted antioxidants, effective preparation methods-including extraction, isolation, and purification of caffeoylquinic acids from plant sources-are in great demand. The aim of this study was to fractionate the caffeoylquinic acids from cultivated wormwood (Artemisia absinthium L.) and silver wormwood (Artemisia ludoviciana Nutt.) herb acetone extracts and evaluate their phytochemical profiles, antioxidant activity (radical scavenging and reducing activities), effects on kidney mitochondrial functions, and cytochrome-c-reducing properties. The main findings of our study are as follows: (1) Aqueous fractions purified from wormwood and silver wormwood herb acetone extracts are rich in monocaffeoylquinic acids (chlorogenic acid, neochlorogenic acid, 4-O-caffeoylquinic acid), while methanolic fractions purified from wormwood and silver wormwood herb acetone extracts are rich in dicaffeoylquinic acids (4,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid). Aqueous fractions purified from wormwood and silver wormwood herb acetone extracts were solely composed of monocaffeoylquinic acids. Methanolic fractions purified from wormwood and silver wormwood herb acetone extracts contained only dicaffeoylquinic acids. (2) Fractions purified from silver wormwood herb acetone extracts stood out as having the greatest content of caffeoylquinic acids. (3) The greatest radical scavenging activity was determined in the dicaffeoylquinic-acid-rich fraction purified from silver wormwood herb acetone extract; the greatest reducing activity was determined in the dicaffeoylquinic-acid-rich fraction purified from wormwood herb acetone extract. (4) The effect of both fractions on mitochondrial functions was dose-dependent; lower concentrations of caffeoylquinic-acid-rich fractions had no effect on mitochondrial functions, whereas higher concentrations of caffeoylquinic-acid-rich fractions reduced the state 3 respiration rate (with the complex-I-dependent substrate glutamate/malate). (5) Both monocaffeoylquinic- and dicaffeoylquinic-acid-rich fractions possessed cytochrome-c-reducing properties; the greatest cytochrome c reduction properties were determined in the dicaffeoylquinic-acid-rich fraction purified from wormwood herb acetone extract. In summary, these findings show that caffeoylquinic acids might be beneficial as promising antioxidant and cytochrome-c-reducing agents for the modulation of mitochondria and treatment of various mitochondrial-pathway-associated pathologies.

Dataset Information

Antimicrobial and efflux pump inhibitory activity of caffeoylquinic acids from Artemisia absinthium against gram-positive pathogenic bacteria.

Publications

Antimicrobial and efflux pump inhibitory activity of caffeoylquinic acids from Artemisia absinthium against gram-positive pathogenic bacteria.

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