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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Detalles Bibliográficos
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
Descripción
Sumario: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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