Abstract Title:

Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase.

Abstract Source:

J Ethnopharmacol. 2011 Jul 1. Epub 2011 Jul 1. PMID: 21782012

Abstract Author(s):

Ben C L Chan, Margaret Ip, Clara B S Lau, S L Lui, Claude Jolivalt, Carine Ganem-Elbaz, Marc Litaudon, Neil E Reiner, Huansheng Gong, Raymond H See, K P Fung, P C Leung

Article Affiliation:

Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry&Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.


ETHNOPHARMACOLOGICAL RELEVANCE: Baicalein, the active constituent derived from Scutellaria baicalensis Georgi., has previously been shown to significantly restore the effectiveness ofβ-lactam antibiotics and tetracycline against methicillin-resistant Staphylococcus aureus (MRSA). With multiple therapeutic benefits, the antibacterial actions of baicalein may also be involved in overcoming other bacterial resistance mechanisms. The aim of the present study was to further investigate antibacterial activities of baicalein in association with various antibiotics against selected Staphylococcus aureus strains with known specific drug resistance mechanisms. MATERIAL AND METHODS: A panel of clinical MRSA strains was used for further confirmation of the antibacterial activities ofbaicalein. The effect of baicalein on inhibiting the enzymatic activity of a newly discovered MRSA-specific pyruvate kinase (PK), which is essential for Staphylococcus aureus growth and survival was also examined. RESULTS: In the checkerboard dilution test and time-kill assay, baicalein at 16μg/mlcould synergistically restore the antibacterial actions of ciprofloxacin against the NorA efflux pump overexpressed SA-1199B, but not with the poor NorA substrate, pefloxacin. Moreover, synergistic effects were observed when baicalein was combined with ciprofloxacin against 12 out of 20 clinical ciprofloxacin resistant strains. For MRSA PK studies, baicalein alone could inhibit the enzymatic activity of MRSA PK in a dose-dependent manner. CONCLUSION: Our results demonstrated that baicalein could significantly reverse the ciprofloxacin resistance of MRSA possibly by inhibiting the NorA effluxpump in vitro. The inhibition of MRSA PK by baicalein could lead to a deficiency of ATP which might further contribute to the antibacterial actions of baicalein against MRSA.

Study Type : In Vitro Study
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Additional Keywords : Drug Synergy : CK(381) : AC(167)

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