title: OXA-143, a novel carbapenem-hydrolyzing class D beta-lactamase in Acinetobacter baumannii.
abstract: A carbapenem-resistant Acinetobacter baumannii strain was isolated in Brazil in 2004 in which no known carbapenemase gene was detected by PCR. Cloning experiments, followed by expression in Escherichia coli, gave an E. coli recombinant strain expressing a novel carbapenem-hydrolyzing class D beta-lactamase (CHDL). OXA-143 showed 88% amino acid sequence identity with OXA-40, 63% identity with OXA-23, and 52% identity with OXA-58. It hydrolyzed penicillins, oxacillin, meropenem, and imipenem but not expanded-spectrum cephalosporins. The bla(OXA-143) gene was located on a ca. 30-kb plasmid. After transformation into reference strain A. baumannii ATCC 19606, it conferred resistance to carbapenems. Analysis of the genetic environment of bla(OXA-143) revealed that it was associated with neither insertion sequences nor integron structures. However, it was bracketed by similar replicase-encoding genes at both ends, suggesting acquisition through a homologous recombination process. This study identified a novel class D beta-lactamase involved in carbapenem resistance in A. baumannii. This enzyme is the first member of a novel subgroup of CHDLs whose prevalence remains to be determined.
authors.affiliation: Institute for Medical Microbiology, Immunology, and Hygiene, University of Cologne, Cologne, Germany. paul.higgins@uni-koeln.de
authors.forename: Paul G
authors.initials: PG
authors.lastname: Higgins
authors.forename: Laurent
authors.initials: L
authors.lastname: Poirel
authors.forename: Marlene
authors.initials: M
authors.lastname: Lehmann
authors.forename: Patrice
authors.initials: P
authors.lastname: Nordmann
authors.forename: Harald
authors.initials: H
authors.lastname: Seifert
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D015780:Carbapenems / Q000378:metabolism* / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics / Q000502:physiology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015378:Imipenem / Q000378:metabolism / Q000494:pharmacology; D000077731:Meropenem; D008969:Molecular Sequence Data; D010068:Oxacillin / Q000378:metabolism / Q000494:pharmacology; D010406:Penicillins / Q000378:metabolism / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013845:Thienamycins / Q000378:metabolism / Q000494:pharmacology; D001618:beta-Lactamases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D010406:Penicillins; D013845:Thienamycins; D015378:Imipenem; C466679:beta-lactamase OXA-23; D001618:beta-Lactamases; C488541:beta-lactamase OXA-40, Acinetobacter baumannii; D000077731:Meropenem; D010068:Oxacillin