BINDING OF THIENAMYCIN AND CLAVULANIC ACID TO PENICILLIN-BINDING PROTEINS OF ESCHERICHIA-COLI K-12
BINDING OF THIENAMYCIN AND CLAVULANIC ACID TO PENICILLIN-BINDING PROTEINS OF ESCHERICHIA-COLI K-12
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DOI：
10.1128/aac.12.3.406
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发表时间：
1977-01-01
影响因子：
4.9
通讯作者：
ZIMMERMAN, W
中科院分区：
文献类型：
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作者：
SPRATT, BG;JOBANPUTRA, V;ZIMMERMAN, W
硫霉素和克拉维酸是新的β-内酰胺衍生物，其结构与青霉素或头孢菌素明显不同。这两种衍生物与典型的β-内酰胺抗生素具有相同的一般作用模式，因为它们与[14C]苄青霉素完全相同的蛋白质结合。硫霉素对青霉素结合蛋白 1、2、4、5 和 6 显示出高亲和力，对蛋白 3 具有较低的亲和力。蛋白 2 对硫霉素具有最高的亲和力，从最小形态变化浓度 (0.1 μg/ml) 到约 0.6 μg/ml 的浓度导致大肠杆菌 KN126 转化为大的渗透稳定的圆形细胞。浓度高于 0.6 μg/ml 时，细胞发生快速裂解，细胞内容物以原生质球形式释放。克拉维酸对青霉素结合蛋白 2 表现出良好的亲和力，对蛋白 1、4、5 和 6 具有中等亲和力，对蛋白 3 具有低亲和力。蛋白 2 对克拉维酸具有最高的亲和力，从最小形态变化浓度 (30 μg/ml) 到约 50 μg/ml 的浓度产生了稍微拉长、肿胀、鼓起和柠檬形细胞的混合物。浓度高于 50 μg/ml 时，会发生快速裂解并产生原生质球。将硫霉素和克拉维酸的性质与青霉素类、头孢菌素类和脒青霉烷酸的性质进行了比较。
Thienamycin and clavulanic acid are new β-lactam derivatives with structures markedly different from those of penicillins or cephalosporins. Both derivatives had the same general mode of action as typical β-lactam antibiotics since they bound to precisely the same proteins as [14C]benzylpenicillin. Thienamycin showed high affinity for penicillin-binding proteins 1, 2, 4, 5, and 6 and a lower affinity for protein 3. Protein 2 had the highest affinity for thienamycin, and concentrations from the minimal morphological change concentration (0.1 μg/ml) up to about 0.6 μg/ml resulted in the conversion ofEscherichia coliKN126 into large osmotically stable round cells. Above a concentration of 0.6 μg/ml, rapid cell lysis occurred with the release of the cell contents as spheroplasts. Clavulanic acid showed good affinity for penicillin-binding protein 2, moderate affinity for proteins 1, 4, 5, and 6, and low affinity for protein 3. Protein 2 had the highest affinity for clavulanic acid, and concentrations from the minimal morphological change concentration (30 μg/ml) up to about 50 μg/ml produced a mixture of slightly elongated, swollen, bulging, and lemon-shaped cells. Above a concentration of 50 μg/ml, rapid lysis occurred with production of spheroplasts. The properties of thienamycin and clavulanic acid were compared with those of the penicillins, cephalosporins, and amidinopenicillanic acids.