title: Molecular and kinetic comparison of the novel extended-spectrum beta-lactamases CTX-M-25 and CTX-M-26.
abstract: CTX-M-25 is a novel extended-spectrum beta-lactamase isolated from a single Canadian Escherichia coli isolate. Susceptibility testing demonstrated that this enzyme confers resistance to both cefotaxime and ceftazidime, but the level of resistance was reduced with the addition of beta-lactamase inhibitors. The bla(CTX-M-25) gene was detected on a 111-kb plasmid. It is a member of the CTX-M-8 group and has the closest amino acid identity (99%; three amino acid substitutions) with CTX-M-26. The bla(CTX-M-26) gene was detected on a 100-kb plasmid isolated from a Klebsiella pneumoniae strain from the United Kingdom, and plasmid profiling revealed that it showed some homology to the bla(CTX-M-25)-harboring plasmid. Both CTX-M genes were located downstream of ISEcp1, although the copy upstream of bla(CTX-M-25) was disrupted by IS50-A. Comparative kinetic studies of recombinant CTX-M-25 and CTX-M-26 enzymes showed that CTX-M-25 has a higher level of ceftazidime hydrolysis (kcat values, 33 and 0.005 s(-1) for CTX-M-25 and CTX-M-26, respectively).
authors.affiliation: Antimicrobial Research Group, Division of Immunity and Infection, The Medical School, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Munday
authors.forename: David A
authors.initials: DA
authors.lastname: Boyd
authors.forename: Nigel
authors.initials: N
authors.lastname: Brenwald
authors.forename: Mark
authors.initials: M
authors.lastname: Miller
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Andrews
authors.forename: Richard
authors.initials: R
authors.lastname: Wise
authors.forename: Michael R
authors.initials: MR
authors.lastname: Mulvey
authors.forename: Peter M
authors.initials: PM
authors.lastname: Hawkey
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015139:Blotting, Southern; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007525:Isoelectric Focusing; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D001618:beta-Lactamases; C495222:beta-lactamase CTX-M-25, E coli; C495223:beta-lactamase CTX-M-26, E coli