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血根碱对耐甲氧西林金黄色葡萄球菌作用机制的研究。

The mechanism of action of sanguinarine against methicillin-resistant Staphylococcus aureus.

机构信息

Wonkwang University, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Jeonbuk 570-749, Korea.

出版信息

J Toxicol Sci. 2011 Jun;36(3):277-83. doi: 10.2131/jts.36.277.

Abstract

Sanguinarine is a benzophenanthridine alkaloid derived from the root of Sanguinaria canadensis. It is known to perform a wide spectrum of biological activities. The aim of this study is to examine the antimicrobial actions of sanguinarine against methicillin-resistant Staphylococcus aureus (MRSA). Sanguinarine antimicrobial activity was assessed by broth dilution method; its mechanism of action was investigated by bacteriolysis, detergent or ATPase inhibitors and transmission electron microscopy were used to monitor the survival characteristics and the changes in bacteria morphology. The activity of sanguinarine against MRSA strains ranged from 3.12 to 6.25 µg/ml, while the minimum inhibitory concentrations of the two reference strains are 3.12 µg/ml and 1.56 µg/ml. The treatment of the cells with sanguinarine induced the release of membrane-bound cell wall autolytic enzymes, which eventually resulted in lysis of the cell. The OD(600s) of the suspensions treated with the combination of Tris-(hydroxymethyl) aminomethane and Triton X-100 with sanguinarine were reduced to 40% and 8%, respectively. Transmission electron microsco-py of MRSA treated with sanguinarine showed alterations in septa formation. The predisposition of lysis and the altered morphology seen by transmission electron microscopy suggest that sanguinarine compromises the cytoplasmic membrane.

摘要

血根碱是一种来源于白屈菜根的苯并菲啶生物碱。它具有广泛的生物活性。本研究旨在研究血根碱对耐甲氧西林金黄色葡萄球菌(MRSA)的抗菌作用。采用肉汤稀释法评估血根碱的抗菌活性;通过溶菌、去污剂或 ATP 酶抑制剂研究其作用机制,并使用透射电子显微镜监测存活特征和细菌形态变化。血根碱对 MRSA 菌株的活性范围为 3.12 至 6.25 µg/ml,而两种参考菌株的最低抑菌浓度为 3.12 µg/ml 和 1.56 µg/ml。用血根碱处理细胞会诱导释放膜结合的细胞壁自溶酶,最终导致细胞裂解。用 Tris-(羟甲基)氨基甲烷和 Triton X-100 与血根碱联合处理的悬浮液的 OD(600s) 分别减少到 40%和 8%。用血根碱处理的 MRSA 的透射电子显微镜显示出隔膜形成的改变。溶菌的倾向和透射电子显微镜观察到的形态改变表明,血根碱破坏了细胞质膜。

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