title: Approved Drugs Containing Thiols as Inhibitors of Metallo-β-lactamases: Strategy To Combat Multidrug-Resistant Bacteria.
abstract: Resistance to β-lactam antibiotics can be mediated by metallo-β-lactamase enzymes (MBLs). An MBL inhibitor could restore the effectiveness of β-lactams. We report on the evaluation of approved thiol-containing drugs as inhibitors of NDM-1, VIM-1, and IMP-7. Drugs were assessed by a novel assay using a purchasable fluorescent substrate and thermal shift. Best compounds were tested in antimicrobial susceptibility assay. Using these orthogonal screening methods, we identified drugs that restored the activity of imipenem.
authors: Franca-M
authors: FM
authors: Klingler
authors: §Institute of Medical Microbiology and Infection Control, Paul-Ehrlich-Straße 40, 60596 Frankfurt, Germany.
authors: Thomas A
authors: TA
authors: Wichelhaus
authors: §Institute of Medical Microbiology and Infection Control, Paul-Ehrlich-Straße 40, 60596 Frankfurt, Germany.
authors: Denia
authors: D
authors: Frank
authors: Jenifer
authors: J
authors: Cuesta-Bernal
authors: Jasmin
authors: J
authors: El-Delik
authors: H Florian
authors: HF
authors: Müller
authors: Hanno
authors: H
authors: Sjuts
authors: §Institute of Medical Microbiology and Infection Control, Paul-Ehrlich-Straße 40, 60596 Frankfurt, Germany.
authors: Stephan
authors: S
authors: Göttig
authors: §Institute of Medical Microbiology and Infection Control, Paul-Ehrlich-Straße 40, 60596 Frankfurt, Germany.
authors: Arno
authors: A
authors: Koenigs
authors: Klaas M
authors: KM
authors: Pos
authors: Denys
authors: D
authors: Pogoryelov
authors: Ewgenij
authors: E
authors: Proschak
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy; D006801:Humans; D015378:Imipenem / Q000494:pharmacology*; D007710:Klebsiella Infections / Q000188:drug therapy; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008958:Models, Molecular; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000494:pharmacology*; D018440:beta-Lactam Resistance / Q000187:drug effects; D065093:beta-Lactamase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D001618:beta-Lactamases / Q000737:chemistry / Q000378:metabolism; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D013438:Sulfhydryl Compounds; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D015378:Imipenem; D001618:beta-Lactamases