Studies on new antimicrobial agents from crude drugs against nosocomial methicillin-resistant Staphylococcus aureus

新型生药抗菌剂抗医院耐甲氧西林金黄色葡萄球菌的研究

• 批准号: 07558095
• 负责人: HIGUTI Tomihiko
• 金额: $ 13.12万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07558095/
• 关键词: highly resistant MRSA; crude drugs; antimicrobial agents; beta-lactam antibiotics; beta-lactam-sensitizers; gallic acid; xanthatin; falvone; 選択毒性; フラボン; MRSA; 半枝蓮; Apigenin; Gallic acid; ガロイル基; 菌体外分泌物質; 訶子; 蒼耳; Ethyl gallate; Xanthatin

To find antimicrobail drugs against methicillin-resistant Staphylococcus aureus (MRSA), crude extracts from plant medicinal resources were screened on the basis of antimicrobial activities against clinical isolates of MRSA and cytotoxic effects against established cell lines of human.From the extracts selected through the screening procecure, 5 effective constituents purified were as follows : gallic acid and ethyl gallate (from Terminalia chebula), xanthatin (from Xanthium sibiricum), apigenia and luteolin (from Scutellaria barbata).Surprisingly, apigenin and luteolin dramatically induced the sensitivity against beta-lactam antibiotics in highly resistant strains of MRSA (MIC,>1000 mug of methicillin/ml). We also found such a synergistic effect by flavone and its related compounds. We named these compounds inducing the sensitivity against beta-lactam antibiotics in MRSA "beta-lactam-sensitizers of MRSA".

为寻找抗耐甲氧西林金黄色葡萄球菌（MRSA）的药物，从植物药用资源中筛选出对MRSA临床分离株有抗菌活性的粗提物和对人成纤维细胞株有细胞毒作用的粗提物，从中分离纯化出5种有效成分：没食子酸和没食子酸乙酯（来自诃子），黄嘌呤（来自Xanthium sibiricum）、芹菜属和木犀草素令人惊讶的是，芹菜素和木犀草素显著诱导MRSA的高度耐药菌株对β-内酰胺类抗生素的敏感性（MIC，>1000 μ g甲氧西林/ml）。我们还发现黄酮及其相关化合物具有协同作用。我们将这些诱导MRSA对β-内酰胺抗生素敏感的化合物命名为“MRSA的β-内酰胺致敏剂”。

项目成果

Sangawa, H., et al.: "Gene Expression of Subunit c(P1),Subunit c(P2), and Oligomycin Sensitivity Conferring Protein May Play a Key Role in Biogenesis of H^+-ATP Synthase in Various Rat Tissues." Journal of Biological Chemistry. 272・9. 6034-6037 (1997)

Sankawa, H. 等人：“亚基 c(P1)、亚基 c(P2) 和寡霉素敏感性赋予蛋白的基因表达可能在各种大鼠组织中 H^+-ATP 合酶的生物合成中发挥关键作用。”生物化学杂志272・9。

Sato, Y., et.al.: "Extraction and Purification of Effective Antimicrobial Constituents of Terminalia chebula Retz.against Methicillin-Resistant Staphylococcus aureus." Biological Pharmaceutical Bulletin. 20・4. 401-404 (1997)

Sato, Y., et.al.：“提取和纯化榄仁树抗耐甲氧西林金黄色葡萄球菌的有效抗菌成分。”生物制药通报 20·4 (1997)。

Sato,Y., et.al.: "A Xanthanolide with Potent Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus." Journal of Pharmacy and Pharmacology. 49・10. 1042-1044 (1997)

Sato, Y., et.al.：“对耐甲氧西林金黄色葡萄球菌具有有效抗菌活性的黄酮内酯。”《药学与药理学杂志》49·10（1997）。

Sato, Y., et al.: "A Xanthanolide with Potent Antibacterial Activity against Methicillin-resistant Staphylococcus aureus." Journal of Pharmacy and Pharmacology. 49・10. 1042-1044 (1997)

Sato, Y., et al.：“对耐甲氧西林金黄色葡萄球菌具有有效抗菌活性的黄酮内酯”，《药学与药理学杂志》49·10（1997）。

Sangawa,H., et.al.: "Gene Expression of Subunit c(P1),Subunit c(P2),and Oligomycin Sensitivity Conferring Protein May Play a Key Role in Biogenesis of H^+-ATP Synthase in Various Rat Tissues." Journal of Biological Chemistry. 272・9. 6034-6037 (1997)

Sankawa, H. 等人：“亚基 c(P1)、亚基 c(P2) 和寡霉素敏感性赋予蛋白的基因表达可能在各种大鼠组织中 H^+-ATP 合酶的生物合成中发挥关键作用。 ” 生物化学杂志. 272・9. 6034-6037 (1997)