title: Correlation of the antimicrobial activity of ME1036 with its binding affinities to the penicillin-binding proteins from Streptococcus pneumoniae strains.
abstract: We have correlated the binding affinities of ME1036, a carbapenem, to the penicillin-binding proteins (PBPs) from Streptococcus pneumoniae strains, with its bactericidal potency against those same strains. Certain mutations in the PBPs from S. pneumonaie strains decrease the binding affinities of β-lactams for PBPs, which gives rise to clinical resistance to those β-lactams. ME1036 has been shown to be strongly active against genotypic penicillin-intermediate S. pneumoniae (gPISP) strains and genotypic penicillin-resistant S. pneumoniae (gPRSP) strains that contain more than one mutation in their PBPs, owing to its strong affinity for those PBPs.
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma, Kanagawa, Japan. youko.hirai@meiji.com
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hirai
authors.forename: Sho
authors.initials: S
authors.lastname: Takahata
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Ida
authors.forename: Kazunori
authors.initials: K
authors.lastname: Maebashi
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology*; D015780:Carbapenems / Q000378:metabolism* / Q000494:pharmacology*; D015169:Colony Count, Microbial; D006801:Humans; D020128:Inhibitory Concentration 50; D050296:Microbial Viability / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D046915:Penicillin-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; C490527:ME1036; D046915:Penicillin-Binding Proteins