title: Interactions of biapenem with active-site serine and metallo-beta-lactamases.
abstract: Biapenem, formerly LJC 10,627 or L-627, a carbapenem antibiotic, was studied in its interactions with 12 beta-lactamases belonging to the four molecular classes proposed by R. P. Ambler (Philos. Trans. R. Soc. Lond. Biol. Sci. 289:321-331, 1980). Kinetic parameters were determined. Biapenem was readily inactivated by metallo-beta-lactamases but behaved as a transient inhibitor of the active-site serine enzymes tested, although with different acylation efficiency values. Class A and class D beta-lactamases were unable to confer in vitro resistance toward this carbapenem antibiotic. Surprisingly, the same situation was found in the case of class B enzymes from Aeromonas hydrophila AE036 and Bacillus cereus 5/B/6 when expressed in Escherichia coli strains.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche e di Biometria, Università degli Studi dell'Aquila, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Felici
authors.forename: M
authors.initials: M
authors.lastname: Perilli
authors.forename: B
authors.initials: B
authors.lastname: Segatore
authors.forename: N
authors.initials: N
authors.lastname: Franceschini
authors.forename: D
authors.initials: D
authors.lastname: Setacci
authors.forename: A
authors.initials: A
authors.lastname: Oratore
authors.forename: S
authors.initials: S
authors.lastname: Stefani
authors.forename: M
authors.initials: M
authors.lastname: Galleni
authors.forename: G
authors.initials: G
authors.lastname: Amicosante
mesh_terms: D001665:Binding Sites; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors; D015378:Imipenem / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008667:Metalloproteins / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D012694:Serine / Q000378:metabolism*; D013845:Thienamycins / Q000378:metabolism* / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000145:classification / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D008667:Metalloproteins; D013845:Thienamycins; D012694:Serine; D015378:Imipenem; D001618:beta-Lactamases; D015032:Zinc; C065257:biapenem