Molecular and biochemical characterization of OXA-45, an extended-spectrum class 2d′ β-lactamase in Pseudomonas aeruginosa

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 β-lactamase genes. One, bla_VIM-7, encoded a metallo-β-lactamase (unpublished data), and the other, bla _OXN-45, described here, encoded a class D extended-spectrum β-lactamase. bla_OXN-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 β-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 β-lactamases.