title: TEM-121, a novel complex mutant of TEM-type beta-lactamase from Enterobacter aerogenes.
abstract: Enterobacter aerogenes clinical isolate LOR was resistant to penicillins and ceftazidime but susceptible to cefuroxime, cephalothin, cefoxitin, cefotaxime, ceftriaxone, and cefepime. PCR and cloning experiments from this strain identified a novel TEM-type beta-lactamase (TEM-121) differing by five amino acid substitutions from beta-lactamase TEM-2 (Glu104Lys, Arg164Ser, Ala237Thr, Glu240Lys, and Arg244Ser) and by only one amino acid change from the extended-spectrum beta-lactamase (ESBL) TEM-24 (Arg244Ser), with the last substitution also being identified in the inhibitor-resistant beta-lactamase IRT-2. Kinetic parameters indicated that TEM-121 hydrolyzed ceftazidime and aztreonam (like TEM-24) and was inhibited weakly by clavulanic acid and strongly by tazobactam. Thus, TEM-121 is a novel complex mutant TEM beta-lactamase (CMT-4) combining the kinetic properties of an ESBL and an inhibitor-resistant TEM enzyme.
authors.affiliation: Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris-Sud, Université Paris XI, Le Kremlin-Bicêtre, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Poirel
authors.forename: Hedi
authors.initials: H
authors.lastname: Mammeri
authors.forename: Patrice
authors.initials: P
authors.lastname: Nordmann
mesh_terms: D002442:Ceftazidime / Q000494:pharmacology*; D018550:Cephalosporin Resistance; D002511:Cephalosporins / Q000494:pharmacology*; D019818:Clavulanic Acid / Q000494:pharmacology; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000096:biosynthesis / Q000235:genetics; D021902:Enterobacter aerogenes / Q000201:enzymology* / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007525:Isoelectric Focusing; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014169:Transformation, Bacterial; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002511:Cephalosporins; D004269:DNA, Bacterial; D004791:Enzyme Inhibitors; D019818:Clavulanic Acid; D002442:Ceftazidime; D001618:beta-Lactamases; C495216:beta-lactamase TEM-121, Enterobacter aerogenes