Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase
Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase
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DOI：
10.1016/j.jep.2011.06.039
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发表时间：
2011-09-01
影响因子：
5.4
通讯作者：
Leung, P. C.
中科院分区：
文献类型：
--
作者：
Chan, Ben C. L.;Ip, Margaret;Leung, P. C.
民族药理学相关性：黄芩素，来自黄芩的活性成分，先前已经显示出显著恢复β-内酰胺抗生素和四环素对耐甲氧西林金黄色葡萄球菌（MRSA）的有效性。具有多种治疗益处，黄芩素的抗菌作用也可能涉及克服其他细菌耐药机制。本研究的目的是进一步探讨黄芩素的抗菌活性与各种抗生素对选定的金黄色葡萄球菌菌株与已知的特定耐药mechanism.Material和方法：一个面板的临床MRSA菌株用于进一步确认黄芩素的抗菌活性。还检测了黄芩素对抑制新发现的MRSA特异性丙酮酸激酶（PK）的酶活性的作用，所述丙酮酸激酶是金黄色葡萄球菌生长和存活所必需的。在棋盘稀释试验和时间杀灭试验中，16 μ g/ml的黄芩素可以协同恢复环丙沙星对过表达SA-1199 B的诺拉外排泵的抗菌作用，但不与不良诺拉底物培氟沙星反应。黄芩素与环丙沙星联用时，对20株环丙沙星耐药菌株中的12株有协同作用。结论：黄芩素能显著逆转MRSA对环丙沙星的耐药性，其机制可能与抑制诺拉外排泵有关。黄芩素对MRSA PK的抑制可能导致ATP缺乏，这可能进一步有助于黄芩素对MRSA的抗菌作用。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Ethnopharmacological relevance: Baicalein, the active constituent derived from Scutellaria baicalensis Georgi., has previously been shown to significantly restore the effectiveness of beta-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 of baicalein. 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 16 mu g/ml could 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 efflux pump 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.