title: Association of the emerging carbapenemase NDM-1 with a bleomycin resistance protein in Enterobacteriaceae and Acinetobacter baumannii.
abstract: The carbapenemase NDM-1 has been identified recently in Enterobacteriaceae and Acinetobacter baumannii as a source of multidrug resistance, including resistance to carbapenems. By analyzing the immediate genetic environment of the bla(NDM-1) carbapenemase gene among a series of NDM-1-producing enterobacterial isolates, a novel gene (ble(MBL), for ble gene associated with the metallo-β-lactamase NDM-1) was identified. The ble(MBL) gene encodes a novel bleomycin resistance protein (BRP), named BRP(MBL), that shares weak similarities with known BRPs (less than 60% amino acid identity). The expression of BRP(MBL) conferred resistance to bleomycin and to bleomycin-like molecules in Enterobacteriaceae and A. baumannii. The bla(NDM-1) and ble(MBL) genes were coexpressed under the control of the same promoter, located upstream of the bla(NDM-1) gene and at the extremity of the insertion sequence ISAba125. Most of the NDM producers possessed the ble(MBL) gene. Although BRP(MBL) did not modify the growth or death rates of Escherichia coli under experimental conditions, it suppressed the mutation rate of hypermutable E. coli and therefore may stabilize the plasmid-borne bla(NDM-1) gene. This study suggests that the emerging carbapenemase NDM-1 is selected by bleomycin-like molecules, and that BRP(MBL) producers (and consequently NDM producers) are better suited to various environments.
authors.affiliation: Service de Bactériologie-Virologie, INSERM U914, Emerging Resistance to Antibiotics, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris Sud, K.-Bicêtre, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Dortet
authors.forename: Patrice
authors.initials: P
authors.lastname: Nordmann
authors.forename: Laurent
authors.initials: L
authors.lastname: Poirel
mesh_terms: D040981:Acinetobacter baumannii / Q000235:genetics*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D001761:Bleomycin / Q000494:pharmacology*; D003470:Culture Media; D017931:DNA Primers; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004755:Enterobacteriaceae / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D015378:Imipenem / Q000494:pharmacology; D007202:Indicators and Reagents; D008826:Microbial Sensitivity Tests; D009154:Mutation; D016366:Open Reading Frames; D009876:Operon / Q000235:genetics; D011401:Promoter Regions, Genetic; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003470:Culture Media; D017931:DNA Primers; D004269:DNA, Bacterial; D007202:Indicators and Reagents; D001761:Bleomycin; C105427:Zeocin; D015378:Imipenem; D001618:beta-Lactamases; C552864:beta-lactamase NDM-1