Neu H C
Am J Med. 1983 Aug 29;75(2A):9-20. doi: 10.1016/0002-9343(83)90089-x.
The activity of penicillins against bacteria is in large part related to binding to specific receptor proteins involved in cell wall biosynthesis. These proteins have been designated penicillin-binding proteins. They can be separated into distinct entities through the use of acrylamide gel electrophoresis and binding of radioactive 14C-labeled penicillin G. Six major proteins have been defined in the Enterobacteriaceae, penicillin-binding proteins 1 to 6. Selection of mutants has shown that there are three essential proteins: penicillin-binding protein 1, which is divided into penicillin-binding protein 1Bs, a peptidoglycan transpeptidase, and penicillin-binding protein 1A, which acts as a replacement for penicillin-binding protein 1Bs. Penicillin-binding protein 2 is a murein-elongation initiating enzyme and penicillin-binding protein 3 is a septal murein-synthesizing enzyme. Penicillin-binding proteins 4, 5, and 6 are not essential for bacterial survival. Binding of penicillins to penicillin-binding protein 1Bs produces lysis, binding to penicillin-binding protein 2 produces round cells, and binding to penicillin-binding protein 3 produces long filaments. Amdinocillin is a beta-amidino penicillanic acid derivative that binds specifically to penicillin-binding protein 2. The compound is more beta-lactamase stable than ampicillin and has no major delay in entry into the periplasmic space as do some penicillins. Amdinocillin inhibits most of the Enterobacteriaceae, with the exception of some indole-positive Proteus species, but it does not inhibit gram-positive cocci or Pseudomonas aeruginosa. Amdinocillin produces spherical bacterial cells that eventually lyse. Its activity in vitro is markedly affected by ionic content of media. This agent acts synergistically with many penicillins, such as ampicillin, carbenicillin, and the like, and with cephalosporins, cefazolin, cefamandole, or cefoxitin to inhibit gram-negative bacilli, probably on the basis of binding to different proteins needed for the production of the peptidoglycan of the bacterial cell wall. Amdinocillin possesses a number of the essentials for effective antimicrobial activity and, by virtue of its enhancement of the activity of other beta-lactams, may prove to be a useful agent in the chemotherapy of certain infections.
青霉素对细菌的活性在很大程度上与结合参与细胞壁生物合成的特定受体蛋白有关。这些蛋白被称为青霉素结合蛋白。通过使用丙烯酰胺凝胶电泳和放射性14C标记的青霉素G的结合，可以将它们分离成不同的实体。在肠杆菌科中已确定了六种主要蛋白，即青霉素结合蛋白1至6。突变体的选择表明有三种必需蛋白：青霉素结合蛋白1，它分为青霉素结合蛋白1Bs（一种肽聚糖转肽酶）和青霉素结合蛋白1A，后者可替代青霉素结合蛋白1Bs。青霉素结合蛋白2是一种胞壁质延伸起始酶，青霉素结合蛋白3是一种隔膜胞壁质合成酶。青霉素结合蛋白4、5和6对细菌存活并非必需。青霉素与青霉素结合蛋白1Bs结合会导致细菌溶解，与青霉素结合蛋白2结合会产生圆形细胞，与青霉素结合蛋白3结合会产生长丝。氨曲南是一种β-脒基青霉烷酸衍生物，它特异性结合青霉素结合蛋白2。该化合物比氨苄西林对β-内酰胺酶更稳定，并且不像某些青霉素那样在进入周质空间时有明显延迟。氨曲南抑制大多数肠杆菌科细菌，但某些吲哚阳性变形杆菌属除外，不过它不抑制革兰氏阳性球菌或铜绿假单胞菌。氨曲南会产生最终溶解的球形细菌细胞。其体外活性受培养基离子含量的显著影响。该药物与许多青霉素（如氨苄西林、羧苄西林等）以及头孢菌素（头孢唑林、头孢孟多或头孢西丁）协同作用以抑制革兰氏阴性杆菌，这可能是基于其与细菌细胞壁肽聚糖生成所需的不同蛋白结合。氨曲南具备有效抗菌活性的多个要素，并且由于它能增强其他β-内酰胺类药物的活性，在某些感染的化疗中可能被证明是一种有用的药物。
