Comparison of two carbapenems, SM-7338 and imipenem: affinities for penicillin-binding proteins and morphological changes.
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.
Sumita
Y
Y
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Fukasawa
M
M
Okuda
T
T
D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006602:Hexosyltransferases; D015378:Imipenem / Q000378:metabolism* / Q000494:pharmacology; D000077731:Meropenem; D008854:Microscopy, Electron; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism*; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D013845:Thienamycins / Q000378:metabolism* / Q000494:pharmacology
D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D013845:Thienamycins; D015378:Imipenem; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D000077731:Meropenem