title: Potent bacteriolytic activity of ritipenem associated with a characteristic profile of affinities for penicillin-binding proteins of Haemophilus influenzae.
abstract: Ritipenem is highly bacteriolytic against Haemophilus influenzae. Bacterial lysis was shown after treatments with ritipenem and cefsulodin at their MICs and after treatments with fropenem and cefdinir at four times their MICs, indicated by decreases in the culture turbidities and by morphological changes of the destroyed cells. These beta-lactams were preferentially bound to penicillin-binding protein (PBP) 1b. Ritipenem, fropenem, and cefsulodin exhibited poor affinities to PBPs 3a and 3b, but cefdinir showed high affinities to these PBPs. Microscopic examinations revealed that selective PBP 3 inhibitors, such as aztreonam and cefotaxime, inhibited lysis induced by ritipenem. These results suggest that the preferential inactivation of PBP 1b could be essential to induce the lysis of H. influenzae cells and that binding to PBPs 3a and 3b may interfere with lysis.
authors.affiliation: Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan. tksh@tanabe.co.jp
authors.forename: T
authors.initials: T
authors.lastname: Inui
authors.forename: T
authors.initials: T
authors.lastname: Oshida
authors.forename: T
authors.initials: T
authors.lastname: Endo
authors.forename: T
authors.initials: T
authors.lastname: Matsushita
mesh_terms: D001426:Bacterial Proteins; D001433:Bacteriolysis / Q000187:drug effects; D015780:Carbapenems / Q000378:metabolism / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism*; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000378:metabolism; D006602:Hexosyltransferases; D006801:Humans; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism*; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases
chemical_list: D001426:Bacterial Proteins; D015780:Carbapenems; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; C040033:ritipenem; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase