Characterization of BRPMBL, the Bleomycin Resistance Protein Associated with the Carbapenemase NDM.

Détails

ID Serval
serval:BIB_94653E8B4B30
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Characterization of BRPMBL, the Bleomycin Resistance Protein Associated with the Carbapenemase NDM.
Périodique
Antimicrobial agents and chemotherapy
Auteur(s)
Dortet L., Girlich D., Virlouvet A.L., Poirel L., Nordmann P., Iorga B.I., Naas T.
ISSN
1098-6596 (Electronic)
ISSN-L
0066-4804
Statut éditorial
Publié
Date de publication
04/2017
Peer-reviewed
Oui
Volume
61
Numéro
3
Pages
e02413-16
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
The metallo-β-lactamase NDM-1 is among the most worrisome resistance determinants and is spreading worldwide among Gram-negative bacilli. A bleomycin resistance gene, bleMBL, downstream of the blaNDM-1 gene has been associated with resistance almost systematically. Here, we characterized the corresponding protein, BRPMBL, conferring resistance to bleomycin, an antitumoral glycopeptide molecule. We have determined whether the expression of the blaNDM-1-bleMBL operon is inducible in the presence of carbapenems and/or bleomycin-like molecules using quantitative reverse transcription-PCR (qRT-PCR), determination of imipenem and zeocin MICs, and carbapenemase-specific activity assays. We showed that the blaNDM-1-bleMBL operon is constitutively expressed. Using electrophoretic mobility shift and DNA protection assays performed with purified glutathione S-transferase (GST)-BRPMBL, we demonstrated that BRPMBL is able to bind and sequester bleomycin-like molecules, thus preventing bleomycin-dependent DNA degradation. In silico modeling confirmed that the mechanism of action required the dimerization of the BRPMBL protein in order to sequester bleomycin and prevent DNA damage. BRPMBL acts specifically on bleomycin-like molecules since cloning and expression of bleMBL in Staphyloccoccus aureus did not confer cross-resistance to any other antimicrobial glycopeptides such as vancomycin and teicoplanin.

Pubmed
Web of science
Création de la notice
17/01/2017 19:28
Dernière modification de la notice
03/03/2018 19:37
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