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New Delhi metallo-β-lactamase-1: structure, inhibitors and detection of producers

    Paul W Groundwater

    *Author for correspondence:

    E-mail Address: paul.groundwater@sydney.edu.au

    Faculty of Pharmacy, The University of Sydney, Camperdown Campus, Sydney, NSW 2006, Australia

    ,
    Sophia Xu

    Faculty of Pharmacy, The University of Sydney, Camperdown Campus, Sydney, NSW 2006, Australia

    ,
    Felcia Lai

    Faculty of Pharmacy, The University of Sydney, Camperdown Campus, Sydney, NSW 2006, Australia

    ,
    Linda Váradi

    Faculty of Pharmacy, The University of Sydney, Camperdown Campus, Sydney, NSW 2006, Australia

    ,
    Jinlong Tan

    Faculty of Pharmacy, The University of Sydney, Camperdown Campus, Sydney, NSW 2006, Australia

    ,
    John D Perry

    Department of Microbiology, Freeman Hospital, Newcastle Upon Tyne, UK

    &
    David E Hibbs

    **Author for correspondence:

    E-mail Address: david.hibbs@sydney.edu.au

    Faculty of Pharmacy, The University of Sydney, Camperdown Campus, Sydney, NSW 2006, Australia

    Published Online:https://doi.org/10.4155/fmc-2016-0015

    Since its discovery in 2008, New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have disseminated globally, facilitated predominantly by gut colonization and the spread of plasmids carrying the blaNDM-1 gene. With few effective antibiotics against NDM-1 producers, and resistance developing to those which remain, there is an urgent need to develop new treatments. To date, most drug design in this area has been focused on developing an NDM-1 inhibitor and has been aided by the wealth of structural and mechanistic information available from high resolution x-ray crystallography and molecular modeling. This review aims to summarize current knowledge regarding the detection of NDM-1 producers, the mechanism of action of NDM-1 and to highlight recent attempts toward the development of clinically useful inhibitors.

    Papers of special note have been highlighted as: •• of considerable interest

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