Synergistic effects of diosmetin with erythromycin against ABC transporter over-expressed methicillin-resistant Staphylococcus aureus (MRSA) RN4220/pUL5054 and inhibition of MRSA pyruvate kinase
| Autor: | Margaret Ip, Neil E. Reiner, Ben Chung-Lap Chan, Sau-Lai Lui, Clara Bik-San Lau, Ping-Chung Leung, Claude Jolivalt, Raymond H. See, Huansheng Gong, Kwok-Pui Fung |
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| Rok vydání: | 2013 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
Pyruvate Kinase Diosmin Pharmaceutical Science Erythromycin Microbial Sensitivity Tests Pharmacology Biology medicine.disease_cause Microbiology chemistry.chemical_compound Adenosine Triphosphate Drug Discovery medicine Flavonoids chemistry.chemical_classification Dose-Response Relationship Drug Drug Synergism biochemical phenomena metabolism and nutrition bacterial infections and mycoses Methicillin-resistant Staphylococcus aureus Diosmetin Anti-Bacterial Agents Enzyme Complementary and alternative medicine chemistry Staphylococcus aureus Molecular Medicine ATP-Binding Cassette Transporters Efflux Pyruvate kinase medicine.drug |
| Zdroj: | Phytomedicine. 20:611-614 |
| ISSN: | 0944-7113 |
| DOI: | 10.1016/j.phymed.2013.02.007 |
| Popis: | Increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) worldwide with limited therapeutic options is a growing public health concern. Natural products have been shown to possess antibacterial actions against MRSA. Flavonoids from natural products have been shown to possess antibacterial actions against MRSA by antagonizing its resistance mechanisms. Diosmin and diosmetin are natural flavonoids found in a variety of citrus fruits. The aim of this study was to investigate whether diosmin and diosmetin could inhibit the growth of MRSA and the in vitro enzymatic activity of a newly discovered MRSA drug target, pyruvate kinase (PK). By using a panel of MRSA strains with known resistant mechanisms, neither diosmin nor diosmetin was shown to possess direct antibacterial activities against all tested MRSA strains. However, in checkerboard assay, we found that diosmetin together with erythromycin, could synergistically inhibit the growth of ABC-pump overexpressed MRSA-RN4220/pUL5054, and time kill assay also showed that the antibacterial activities of diosmetin with erythromycin were bactericidal. Diosmetin was further shown to significantly suppress the MRSA PK activities in a dose dependent manner. In conclusion, the inhibition of MRSA PK by diosmetin could lead to a deficiency of ATP and affect the bacterial efflux pump which might contribute to the antibacterial actions of diosmetin against MRSA. |
| Databáze: | OpenAIRE |
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