title: 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.
authors.affiliation: Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Tsukuba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hashizume
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Nakagawa
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D015780:Carbapenems / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006602:Hexosyltransferases; D007700:Kinetics; D016106:Methicillin Resistance; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism*; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000378:metabolism*; D010458:Peptidyl Transferases; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D001426:Bacterial Proteins; D015780:Carbapenems; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; C085890:BO 2727; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase