title: CTX-M-type extended-spectrum beta-lactamase that hydrolyzes ceftazidime through a single amino acid substitution in the omega loop.
abstract: Escherichia coli ILT-1, Klebsiella pneumoniae ILT-2, and K. pneumoniae ILT-3 were isolated in May 1999 in Paris, France, from a rectal swab of a hospitalized 5-month-old girl. These isolates had a clavulanic acid-inhibited substrate profile that included expanded-spectrum cephalosporins. The MICs of cefotaxime were higher for E. coli ILT-1 and K. pneumoniae ILT-2 than for K. pneumoniae ILT-3, while the opposite was found for the MICs of ceftazidime. Genetic and biochemical analyses revealed that E. coli ILT-1 and K. pneumoniae ILT-2 produced the CTX-M-18 beta-lactamase, while K. pneumoniae ILT-3 produced the CTX-M-19 beta-lactamase. The amino acid sequence of the CTX-M-18 beta-lactamase differed from that of the CTX-M-9 beta-lactamase by an Ala-to-Val change at position 231, while CTX-M-19 possessed an additional Pro-to-Ser change at position 167 in the omega loop of Ambler class A enzymes. The latter amino acid substitution may explain the CTX-M-19-mediated hydrolysis of ceftazidime, which has not been reported for other CTX-M-type enzymes. The bla(CTX-M-18) and bla(CTX-M-19) genes were located on transferable plasmids that varied in size (ca. 60 and 50 kb, respectively) but that showed similar restriction patterns.
authors.affiliation: Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris-Sud, 94275 Le Kremlin-Bicêtre Cedex, France.
authors.forename: L
authors.initials: L
authors.lastname: Poirel
authors.forename: T
authors.initials: T
authors.lastname: Naas
authors.forename: I
authors.initials: I
authors.lastname: Le Thomas
authors.forename: A
authors.initials: A
authors.lastname: Karim
authors.forename: E
authors.initials: E
authors.lastname: Bingen
authors.forename: P
authors.initials: P
authors.lastname: Nordmann
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002442:Ceftazidime / Q000378:metabolism*; D002511:Cephalosporins / Q000378:metabolism*; D004269:DNA, Bacterial / Q000235:genetics; D006824:Hybridization, Genetic; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D002511:Cephalosporins; D004269:DNA, Bacterial; D011994:Recombinant Proteins; D002442:Ceftazidime; C071167:beta-lactamase CTX-2; D001618:beta-Lactamases