Fujita Mai, Shiota Sumiko, Kuroda Teruo, Hatano Tsutomu, Yoshida Takashi, Mizushima Tohru, Tsuchiya Tomofusa
Department of Microbiology, Faculty of Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Microbiol Immunol. 2005;49(4):391-6. doi: 10.1111/j.1348-0421.2005.tb03732.x.
During the screening of compounds that potentiate the effect of antimicrobial agents against methicillin-resistant Staphylococcus aureus(MRSA), we found that an extract of thyme (Thymus vulgaris L) leaves greatly reduced the minimum inhibitory concentration (MIC) of tetracycline against MRSA. We isolated the effective compound and identified it as baicalein (5, 6, 7-trihydroxyflavone). One of the clinically isolated MRSA strains possessed tetK, a gene encoding active efflux pump for tetracycline. We examined the effect of baicalein on the efflux of tetracycline, using Escherichia coli KAM32/pTZ1252 carrying the tetK. The E. coli KAM32/pTZ1252 showed 8 to 16 times higher MIC than E. coli KAM32. We observed strong inhibition of transport of tetracycline by baicalein with membrane vesicles prepared from E. coli KAM32/pTZ1252. Baicalein also showed synergy with tetracycline in a MRSA strain that doesn't possess tetK, or with beta-lactams. Thus, mechanisms of the synergies seem to be versatile.
在筛选增强抗菌剂对耐甲氧西林金黄色葡萄球菌（MRSA）作用的化合物时，我们发现百里香叶提取物大大降低了四环素对MRSA的最低抑菌浓度（MIC）。我们分离出有效化合物并鉴定为黄芩素（5,6,7 - 三羟基黄酮）。临床分离的一株MRSA菌株携带tetK，这是一个编码四环素活性外排泵的基因。我们使用携带tetK的大肠杆菌KAM32/pTZ1252研究了黄芩素对四环素外排的影响。大肠杆菌KAM32/pTZ1252的MIC比大肠杆菌KAM32高8至16倍。我们观察到黄芩素对从大肠杆菌KAM32/pTZ1252制备的膜囊泡中四环素的转运有强烈抑制作用。黄芩素在不携带tetK的MRSA菌株中也与四环素显示出协同作用，或者与β - 内酰胺类药物显示出协同作用。因此，协同作用的机制似乎是多样的。
