New boronate drugs and evolving NDM-mediated beta-lactam resistance

Taniborbactam and xeruborbactam are dual serine-/metallo-beta-lactamase inhibitors (BLIs) based on a cyclic boronic acid pharmacophore that undergo clinical development. Recent report demonstrated that New Delhi metallo-beta-lactamase (NDM)-9 (differs from NDM-1 by a single amino acid substitution,...

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Autores principales: Lomovskaya, Olga, Tsivkovski, Ruslan, Totrov, Maxim, Dressel, Dana, Castanheira, Mariana, Dudley, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Mechanisms of Resistance
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10508144/
https://www.ncbi.nlm.nih.gov/pubmed/37650617
http://dx.doi.org/10.1128/aac.00579-23
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author Lomovskaya, Olga
Tsivkovski, Ruslan
Totrov, Maxim
Dressel, Dana
Castanheira, Mariana
Dudley, Michael
author_facet Lomovskaya, Olga
Tsivkovski, Ruslan
Totrov, Maxim
Dressel, Dana
Castanheira, Mariana
Dudley, Michael
author_sort Lomovskaya, Olga
collection PubMed
description Taniborbactam and xeruborbactam are dual serine-/metallo-beta-lactamase inhibitors (BLIs) based on a cyclic boronic acid pharmacophore that undergo clinical development. Recent report demonstrated that New Delhi metallo-beta-lactamase (NDM)-9 (differs from NDM-1 by a single amino acid substitution, E152K, evolved to overcome Zn (II) deprivation) is resistant to inhibition by taniborbactam constituting pre-existing taniborbactam resistance mechanism. Using microbiological and biochemical experiments, we show that xeruborbactam is capable of inhibiting NDM-9 and propose the structural basis for differences between two BLIs.
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spelling pubmed-105081442023-09-20 New boronate drugs and evolving NDM-mediated beta-lactam resistance Lomovskaya, Olga Tsivkovski, Ruslan Totrov, Maxim Dressel, Dana Castanheira, Mariana Dudley, Michael Antimicrob Agents Chemother Mechanisms of Resistance Taniborbactam and xeruborbactam are dual serine-/metallo-beta-lactamase inhibitors (BLIs) based on a cyclic boronic acid pharmacophore that undergo clinical development. Recent report demonstrated that New Delhi metallo-beta-lactamase (NDM)-9 (differs from NDM-1 by a single amino acid substitution, E152K, evolved to overcome Zn (II) deprivation) is resistant to inhibition by taniborbactam constituting pre-existing taniborbactam resistance mechanism. Using microbiological and biochemical experiments, we show that xeruborbactam is capable of inhibiting NDM-9 and propose the structural basis for differences between two BLIs. American Society for Microbiology 2023-08-31 /pmc/articles/PMC10508144/ /pubmed/37650617 http://dx.doi.org/10.1128/aac.00579-23 Text en Copyright © 2023 Lomovskaya et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Mechanisms of Resistance
Lomovskaya, Olga
Tsivkovski, Ruslan
Totrov, Maxim
Dressel, Dana
Castanheira, Mariana
Dudley, Michael
New boronate drugs and evolving NDM-mediated beta-lactam resistance
title New boronate drugs and evolving NDM-mediated beta-lactam resistance
title_full New boronate drugs and evolving NDM-mediated beta-lactam resistance
title_fullStr New boronate drugs and evolving NDM-mediated beta-lactam resistance
title_full_unstemmed New boronate drugs and evolving NDM-mediated beta-lactam resistance
title_short New boronate drugs and evolving NDM-mediated beta-lactam resistance
title_sort new boronate drugs and evolving ndm-mediated beta-lactam resistance
topic Mechanisms of Resistance
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10508144/
https://www.ncbi.nlm.nih.gov/pubmed/37650617
http://dx.doi.org/10.1128/aac.00579-23
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