title: Six groups of the OXY beta-Lactamase evolved over millions of years in Klebsiella oxytoca.
abstract: The diversity and evolution of the class A OXY beta-lactamase from Klebsiella oxytoca were investigated and compared to housekeeping gene diversity. The entire bla(OXY) coding region was sequenced in 18 clinical isolates representative of the four K. oxytoca beta-lactamase gene groups bla(OXY-1) to bla(OXY-4) and of two new groups identified here, bla(OXY-5) (with four isolates with pI 7.2 and one with pI 7.7) and bla(OXY-6) (with four isolates with pI 7.75 and three with pI 8.1). Genes bla(OXY-5) and bla(OXY-6) showed 99.8% within-group nucleotide similarity but differed from each other by 4.2% and from bla(OXY-1), their closest relative, by 2.5% and 2.9%, respectively. Antimicrobial susceptibility to beta-lactams was similar among OXY groups. Nucleotide sequence diversity of the 16S rRNA (1,454 bp), rpoB (940 bp), gyrA (383 bp), and gapDH (573 bp) genes was in agreement with the beta-lactamase gene phylogeny. Strains with bla(OXY-1), bla(OXY-2), bla(OXY-3), bla(OXY-4), and bla(OXY-6) genes formed five phylogenetic groups, named KoI, KoII, KoIII, KoIV, and KoVI, respectively. Isolates harboring bla(OXY-5) appeared to represent an emerging lineage within KoI. We estimated that the bla(OXY) gene has been evolving within K. oxytoca for approximately 100 million years, using as calibration the 140-million-year estimation of the Escherichia coli-Salmonella enterica split. These results show that the bla(OXY) gene has diversified along K. oxytoca phylogenetic lines over long periods of time without concomitant evolution of the antimicrobial resistance phenotype.
authors.affiliation: Unité Biodiversité des Bactéries Pathogènes Emergentes (U389 INSERM), Institut Pasteur, 25-28 rue du Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Fevre
authors.forename: Mehdi
authors.initials: M
authors.lastname: Jbel
authors.forename: Virginie
authors.initials: V
authors.lastname: Passet
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Weill
authors.forename: Patrick A D
authors.initials: PA
authors.lastname: Grimont
authors.forename: Sylvain
authors.initials: S
authors.lastname: Brisse
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics; D024881:Drug Resistance, Bacterial; D019143:Evolution, Molecular; D006801:Humans; D007525:Isoelectric Focusing; D041121:Klebsiella oxytoca / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D001618:beta-Lactamases / Q000737:chemistry / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D047090:beta-Lactams; D001618:beta-Lactamases