title: Kinetic properties of two plasmid-mediated beta-lactamases from Klebsiella pneumoniae with strong activity against third-generation cephalosporins.
abstract: We determined the kinetic constants for two plasmid-mediated beta-lactamases with strong activity against third-generation cephalosporins: CTX-1 and SHV-2. The enzymes had many similar properties: their synthesis was constitutive and they were significantly active against penicillins as well as cephalosporins. The two enzymes thus differed considerably from the chromosomal cephalosporinases, but bore some resemblance to the commonly-encountered plasmid-coded penicillinases, such as TEM beta-lactamases. Moreover, like the TEM enzymes, the plasmid-mediated CTX-1 and SHV-2 enzymes were highly sensitive to the action of the inhibitors clavulanic acid and sulbactam. These inhibitors protected cefotaxime from hydrolysis by these enzymes. Both CTX-1 and SHV-2 lacked activity against the cephamycins, cefoxitin, latamoxef (moxalactam) and cefotetan. The CTX-1 and SHV-2 enzymes had a low activity against oxacillin and were not sensitive to chloride ions. Thus, they were not related to the OXA type beta-lactamases. For the third-generation cephalosporins the rates of hydrolysis were high and thus bore no relation with those observed for the other presently-known beta-lactamases, with perhaps the exceptions of those produced by K. oxytoca. Imipenem was very resistant to the action of these CTX-1 and SHV-2 beta-lactamases.
authors.affiliation: Muséum National d'Histoire Naturelle, UA 401 CNRS, 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 S
authors.initials: JS
authors.lastname: Pitton
authors.forename: D
authors.initials: D
authors.lastname: Sirot
authors.forename: J
authors.initials: J
authors.lastname: Sirot
mesh_terms: D002511:Cephalosporins / Q000378:metabolism*; D004352:Drug Resistance, Microbial; D006868:Hydrolysis; D007700:Kinetics; D007711:Klebsiella pneumoniae / Q000201:enzymology*; D010957:Plasmids; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000032:analysis*
chemical_list: D002511:Cephalosporins; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases