title: New Delhi metallo-β-lactamase-1: structure, inhibitors and detection of producers.
abstract: 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 bla NDM-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.
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Camperdown Campus, Sydney, NSW 2006, Australia.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Groundwater
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Camperdown Campus, Sydney, NSW 2006, Australia.
authors.forename: Sophia
authors.initials: S
authors.lastname: Xu
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Camperdown Campus, Sydney, NSW 2006, Australia.
authors.forename: Felcia
authors.initials: F
authors.lastname: Lai
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Camperdown Campus, Sydney, NSW 2006, Australia.
authors.forename: Linda
authors.initials: L
authors.lastname: Váradi
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Camperdown Campus, Sydney, NSW 2006, Australia.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Microbiology, Freeman Hospital, Newcastle Upon Tyne, UK.
authors.forename: John D
authors.initials: JD
authors.lastname: Perry
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Camperdown Campus, Sydney, NSW 2006, Australia.
authors.forename: David E
authors.initials: DE
authors.lastname: Hibbs
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D001618:beta-Lactamases / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D001618:beta-Lactamases; C552864:beta-lactamase NDM-1
keywords: Enterobacteriaceae; NDM-1; New Delhi metallo-β-lactamase-1; detection; inhibitors; mechanism; substrates