Affinities of BO-2727 for bacterial penicillin-binding proteins and morphological change of gram-negative rods

Abstract

Affinities of BO-2727, a new carbapenem for penicillin-binding proteins (PBPs) of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. were studied. BO-2727 showed preferential affinity for PBP-2 of E. coli, and induced swollen and ovoid cells, when the organism was exposed to the MIC. In contrast, BO-2727 bound to both PBPs-2 and -3 of P. aeruginosa to a similar extent, and induced short filament cells with bulge. As compared with imipenem and meropenem, there was an observed difference in the affinity, especially for PBP-3, in both organisms; BO-2727 displayed intermediate affinity for PBP-3 between meropenem and imipenem. Studies on the affinity for PBPs of methicillin-susceptible S. aureus showed that the IC50 values for PBP-1 was roughly correlated with the MIC values of carbapenems tested, but those for the PBPs-2 and -3 appeared to be greater than the MIC values. In further studies on the affinity for PBP-2' of methicillin-resistant S. aureus, BO-2727 displayed better binding kinetics than imipenem, which reflected the better activity of. BO-2727 than that of imipenem.