Approved Drugs Containing Thiols as Inhibitors of Metallo-β-lactamases: Strategy To Combat Multidrug-Resistant Bacteria
journal contribution
posted on 2015-04-23, 00:00 authored by Franca-M. Klingler, Thomas
A. Wichelhaus, Denia Frank, Jenifer Cuesta-Bernal, Jasmin El-Delik, H. Florian Müller, Hanno Sjuts, Stephan Göttig, Arno Koenigs, Klaas M. Pos, Denys Pogoryelov, Ewgenij ProschakResistance
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.
