Synergistic effects of diosmetin with erythromycin against ABC transporter over-expressed methicillin-resistant Staphylococcus aureus (MRSA) RN4220/pUL5054 and inhibition of MRSA pyruvate kinase
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摘要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. (c) 2013 Elsevier GmbH. All rights reserved.
著者Chan BCL, Ip M, Gong H, Lui SL, See RH, Jolivalt C, Fung KP, Leung PC, Reiner NE, Lau CBS
期刊名稱Phytomedicine
出版年份2013
月份5
日期15
卷號20
期次7
出版社Elsevier
頁次611 - 614
國際標準期刊號0944-7113
電子國際標準期刊號1618-095X
語言英式英語
關鍵詞Diosmetin; Diosmin; Methicillin-resistant Staphylococcus aureus; Pyruvate kinase; Synergy
Web of Science 學科類別Chemistry, Medicinal; CHEMISTRY, MEDICINAL; Integrative & Complementary Medicine; INTEGRATIVE & COMPLEMENTARY MEDICINE; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY; Plant Sciences; PLANT SCIENCES

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