Sumita Y, Fukasawa M, Okuda T
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
J Antibiot (Tokyo). 1990 Mar;43(3):314-20. doi: 10.7164/antibiotics.43.314.
We investigated the binding affinities of SM-7338 for penicillin-binding proteins (PBPs) and the morphological changes induced by it compared with those of imipenem. Both SM-7338 and imipenem had the highest binding affinities for PBP-2 of Escherichia coli, which were in good agreement with the primary morphological response of spherical cell formation. SM-7338 also showed high affinities for PBP-1A, -1Bs, and -3, and imipenem showed high affinities for PBP-1A and -1Bs but not for PBP-3. At 4-fold MIC, SM-7338 induced a indeterminate form, whereas imipenem did not. This may be due to the higher affinity of SM-7338 for PBP-3 compared to that of imipenem. Against Pseudomonas aeruginosa, SM-7338 had very high affinities for PBP-2 and -3, and imipenem had higher affinities for PBP-2 and -1A. SM-7338 induced this organism to filamentous cells at a concentration lower than its MIC, bulge cells at 2-fold MIC, and spherical cells at 4-fold MIC, while imipenem principally induced round cell formation at each concentration. These morphological differences in P. aeruginosa may be due to the differences in binding profiles to PBPs. We also studied the affinities for PBPs using radioactive SM-7338. The data obtained supported these results.
我们研究了SM-7338与青霉素结合蛋白（PBPs）的结合亲和力，以及与亚胺培南相比它所诱导的形态学变化。SM-7338和亚胺培南对大肠杆菌的PBP-2具有最高的结合亲和力，这与球形细胞形成的主要形态学反应高度一致。SM-7338对PBP-1A、-1Bs和-3也表现出高亲和力，而亚胺培南对PBP-1A和-1Bs表现出高亲和力，但对PBP-3没有。在4倍MIC时，SM-7338诱导出一种不确定形态，而亚胺培南则没有。这可能是由于SM-7338对PBP-3的亲和力高于亚胺培南。对于铜绿假单胞菌，SM-7338对PBP-2和-3具有非常高的亲和力，亚胺培南对PBP-2和-1A具有更高的亲和力。SM-7338在低于其MIC的浓度下诱导该菌形成丝状细胞，在2倍MIC时形成凸起细胞，在4倍MIC时形成球形细胞，而亚胺培南在各浓度下主要诱导圆形细胞形成。铜绿假单胞菌的这些形态学差异可能归因于与PBPs结合谱的差异。我们还使用放射性SM-7338研究了对PBPs的亲和力。获得的数据支持了这些结果。
