title: Interactions of new plasmid-mediated beta-lactamases with third-generation cephalosporins.
abstract: The kinetic constants of three recently identified plasmid-mediated beta-lactamases--SHV-2, CTX-1, and CAZ-1--markedly active against third-generation cephalosporins were analyzed in comparison with three better-characterized beta-lactamases--two plasmid-mediated enzymes, TEM-2 and PIT-2/SHV-1, and R-30, a beta-lactamase from Klebsiella oxytoca that has few similarities to the newer enzymes. All of these enzymes are synthesized constitutively, demonstrate efficient hydrolysis of penicillins, are highly susceptible to the action of clavulanic acid and sulbactam, and have no detectable activity against the cephamycins and imipenem. With the methoxyimino cephalosporins, including those of the third generation, the rates of hydrolysis observed for the SHV-2, CTX-1, and CAZ-1 enzymes are high and show no relation to those observed for the other presently known beta-lactamases. Structure-activity relations suggest that the oxime substituent of these cephalosporins is a major structural factor in the catalytic process observed with the three new beta-lactamases.
authors.affiliation: Muséum National d'Histoire Naturelle, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Labia
authors.forename: A
authors.initials: A
authors.lastname: Morand
authors.forename: K
authors.initials: K
authors.lastname: Tiwari
authors.forename: J
authors.initials: J
authors.lastname: Sirot
authors.forename: D
authors.initials: D
authors.lastname: Sirot
authors.forename: A
authors.initials: A
authors.lastname: Petit
mesh_terms: D002511:Cephalosporins / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D006868:Hydrolysis; D007700:Kinetics; D007709:Klebsiella / Q000201:enzymology* / Q000235:genetics; D010957:Plasmids; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D002511:Cephalosporins; D001618:beta-Lactamases