Restoring Meropenem Activity Against VIM-1-Producing Klebsiella pneumoniae Through Zinc-Binding Ligands.

Authors

Chiara Ragusa, Ruqaiya Khalil, Valentina Giglio, Kaveh Eskandari, Fraser J Scott, Attilio V Vargiu, Graziella Vecchio

Published in

Chembiochem : a European journal of chemical biology. Volume 27. Issue 16. Pages e70509. Aug 27, 2026.

Abstract

The growing prevalence of metallo-β-lactamase (MBL)-producing bacteria threatens the clinical efficacy of carbapenems such as meropenem. To investigate potential strategies for restoring β-lactam activity, a panel of compounds was evaluated as putative MBL inhibitors and antibiotic adjuvants. The panel included FDA-approved drugs (carbonic anhydrase inhibitors, an antiviral agent, and a metal chelator), and two novel histidine-pyridine derivatives (D- and L-2-amino-3-(1H-imidazol-4-yl)-N-[2-(pyridin-2-yl)ethyl]propenamides). The latter were synthesized and characterized by NMR spectroscopy and mass spectrometry. Combination assays against Verona Integron-encoded Metallo-β-Lactamase 1 (VIM-1)-producing Klebsiella pneumoniae showed that D-penicillamine and chlorpropamide restored meropenem activity. These effects were supported by time-dependent inhibition and checkerboard assays. Molecular docking and MD simulations with the VIM-1 enzyme further elucidated the putative binding modes of these inhibitors. These results suggest that repurposing the conventional D-penicillamine and chlorpropamide drugs can effectively counteract MBL-mediated resistance.

PMID:
42644634
Bibliographic data and abstract were imported from PubMed on 26 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.