title: Molecular and biochemical characterization of OXA-45, an extended-spectrum class 2d' beta-lactamase in Pseudomonas aeruginosa.
abstract: As part of the CANCER Antimicrobial Surveillance Program in North America, a clinical strain of Pseudomonas aeruginosa, strain 07-406, isolated in Texas was found to be resistant to all antimicrobials except polymyxin B. Genetic analysis of this isolate identified two unique extended-spectrum beta-lactamase genes. One, bla(VIM-7), encoded a metallo-beta-lactamase (unpublished data), and the other, bla(OXA-45), described here, encoded a class D extended-spectrum beta-lactamase. bla(OXA-45) was isolated on a Sau3A1 genomic fragment of 1.8 kb and encodes a protein of 264 amino acids with the highest identities to OXA-18 (65.9%), OXA-9 (42.8%), OXA-22 (40.2%), OXA-12 (38.6%), and OXA-29 (35.2%) but weak identities with other class D beta-lactamases. bla(OXA-45) was found to be harbored on a 24-kb plasmid in a region that displays high identities with a section of the 43-kb genomic island of Salmonella enterica serovar Typhimurium DT104. Biochemically OXA-45 is most similar to OXA-18 in its substrate profile and inhibition by clavulanic acid and is a member of the 2d' class of beta-lactamases.
authors.affiliation: Department of Pathology and Microbiology, University of Bristol, Bristol BS8 1TD, United Kingdom. Mark.Toleman@bristol.ac.uk
authors.forename: Mark A
authors.initials: MA
authors.lastname: Toleman
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rolston
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Walsh
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001398:Aztreonam / Q000494:pharmacology; D003001:Cloning, Molecular; D017931:DNA Primers; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D007525:Isoelectric Focusing; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D008997:Monobactams / Q000494:pharmacology; D010068:Oxacillin / Q000494:pharmacology; D010403:Penicillin Resistance / Q000235:genetics; D010406:Penicillins / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D011112:Polymyxin B / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001618:beta-Lactamases / Q000737:chemistry / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D017931:DNA Primers; D004269:DNA, Bacterial; D008997:Monobactams; D010406:Penicillins; D001618:beta-Lactamases; C477885:beta-lactamase OXA-45, Pseudomonas aeruginosa; D001398:Aztreonam; D011112:Polymyxin B; D010068:Oxacillin