Rake J B, Newman D J, Actor P
J Antibiot (Tokyo). 1984 May;37(5):572-6. doi: 10.7164/antibiotics.37.572.
The binding of cefonicid (SK&F 75073), a new parenteral cephalosporin, to the penicillin-binding proteins (PBPs) of Escherichia coli K-12 (strain KN-126) was determined by competitive binding studies versus benzyl[14C]penicillin. Cefonicid showed its greatest affinity for PBPs 1a greater than 3 greater than 1b, bound with low affinity to PBPs 4 greater than 2, and did not bind to PBPs 5 and 6. Provisional affinity constants (cefonicid concentration that gave 50% inhibition of [14C]penicillin binding) were determined: PBP 1a, less than 0.25 microgram/ml; PBP 3, 0.7 microgram/ml; PBP 1b, 10 micrograms/ml; PBP 4, 26 micrograms/ml; PBP 2, 90 micrograms/ml; PBPs 5 and 6 greater than 256 micrograms/ml. Direct binding studies with [14C]-cefonicid confirmed this pattern of binding. Subinhibitory concentrations of cefonicid (MIC, broth 0.2 microgram/ml, agar 0.4 microgram/ml) induced filamentation of E. coli KN-126. This implies that PBP 3 is the primary inhibitory site despite the higher affinity of PBP 1a for this cephalosporin.
通过与苄基[14C]青霉素进行竞争性结合研究，测定了一种新型胃肠外头孢菌素头孢尼西（SK&F 75073）与大肠杆菌K-12（菌株KN-126）青霉素结合蛋白（PBPs）的结合情况。头孢尼西对PBPs 1a的亲和力最高，其次是3，然后是1b；与PBPs 4的结合亲和力较低，其次是2；且不与PBPs 5和6结合。测定了临时亲和力常数（导致[14C]青霉素结合被50%抑制的头孢尼西浓度）：PBP 1a，小于0.25微克/毫升；PBP 3，0.7微克/毫升；PBP 1b，10微克/毫升；PBP 4，26微克/毫升；PBP 2，90微克/毫升；PBPs 5和6大于256微克/毫升。用[14C] - 头孢尼西进行的直接结合研究证实了这种结合模式。亚抑菌浓度的头孢尼西（肉汤中的最低抑菌浓度为0.2微克/毫升，琼脂中的最低抑菌浓度为0.4微克/毫升）诱导大肠杆菌KN-126形成丝状体。这意味着尽管PBP 1a对这种头孢菌素的亲和力更高，但PBP 3是主要的抑制位点。
