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

ABSTRACT: 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.

SUBMITTER: Lomovskaya O

PROVIDER: S-EPMC10508144 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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

Lomovskaya Olga O Tsivkovski Ruslan R Totrov Maxim M Dressel Dana D Castanheira Mariana M Dudley Michael M

Antimicrobial agents and chemotherapy 20230831 9

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 experime ...[more]

PMID: 37650617

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