Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 56, Issue 4, Pages 1693-1697Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.05583-11
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Funding
- INSERM [U914]
- Ministere de l'Education Nationale et de la Recherche [UPRES-EA3539]
- Universite Paris XI, France
- European Community [241742]
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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-beta-lactamase NDM-1) was identified. The ble(MBL) gene encodes a novel bleomycin resistance protein (BRP), named BRPMBL, that shares weak similarities with known BRPs (less than 60% amino acid identity). The expression of BRPMBL 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 BRPMBL 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 BRPMBL producers (and consequently NDM producers) are better suited to various environments.
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