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Antimicrobial and efflux pump inhibitory activity of caffeoylquinic acids from Artemisia absinthium against gram-positive pathogenic bacteria.
- Source :
-
PloS one [PLoS One] 2011 Apr 04; Vol. 6 (4), pp. e18127. Date of Electronic Publication: 2011 Apr 04. - Publication Year :
- 2011
-
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.<br />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.<br />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.
- Subjects :
- ATP-Binding Cassette Transporters chemistry
ATP-Binding Cassette Transporters metabolism
Animals
Anti-Bacterial Agents pharmacology
Anti-Infective Agents chemistry
Anti-Infective Agents toxicity
Berberine metabolism
Biofilms drug effects
Drug Synergism
Gram-Positive Bacteria metabolism
Gram-Positive Bacteria physiology
Hemolysis drug effects
Humans
Models, Molecular
Plant Extracts chemistry
Plant Extracts pharmacology
Plant Extracts toxicity
Protein Conformation
Quinic Acid chemistry
Quinic Acid pharmacology
Quinic Acid toxicity
Anti-Infective Agents pharmacology
Artemisia absinthium chemistry
Drug Resistance, Multiple drug effects
Gram-Positive Bacteria drug effects
Quinic Acid analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 6
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 21483731
- Full Text :
- https://doi.org/10.1371/journal.pone.0018127