title: Comparison of activities of beta-lactam antibiotics against Streptococcus pneumoniae with recombinant penicillin-binding protein genes from a penicillin-resistant strain.
abstract: We investigated the antibacterial activities of 19 beta-lactams against three recombinant bacterial strains, in which three penicillin-binding protein genes, pbp2x, pbp1a, and pbp2b, from penicillin-resistant Streptococcus pneumoniae (PRSP), were transformed to a penicillin-susceptible strain. By the acquisition of the pbp2x gene from PRSP, the minimum inhibitory concentrations (MICs) of third-generation cephalosporins were increased more than eight fold. When the strain acquired the PRSP pbp1a gene in addition to pbp2x, the MICs of all tested beta-lactams increased 2- to 16-fold. When the strain acquired the PRSP pbp2b gene in addition to pbp2x and pbp1a, the MICs of penicillins and carbapenems increased 4- to 16-fold. However, two novel carbapenems, ME1036 and L-036, showed excellent antibacterial activities against these recombinant strains, as well as against the parent PRSP.
authors.affiliation: Pharmaceutical Research Department, Meiji Seika Kaisha Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, 222-8567, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Maeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Ida
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Sanbongi
authors.forename: Takahisa
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Fukushima
authors.forename: Mizuyo
authors.initials: M
authors.lastname: Kurazono
authors.forename: Minoru
authors.initials: M
authors.lastname: Yonezawa
authors.forename: Kimiko
authors.initials: K
authors.lastname: Ubukata
authors.forename: Matsuhisa
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010403:Penicillin Resistance; D046915:Penicillin-Binding Proteins / Q000235:genetics*; D011995:Recombination, Genetic; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D046915:Penicillin-Binding Proteins; D047090:beta-Lactams