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April 3, 2026Journal of Antimicrobial Chemotherapy0 citationsOpen Access

Metallo-β-lactamase–producing Enterobacterales: cyanide-containing efflux pump inhibitors as potential dual-activity inhibitors

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OROtávio Hallal Ferreira RaroCSCsaba SzaboPNPatrice Nordmann

Key Points

  • The research aims to explore the potential of cyanide-containing compounds as inhibitors of metallo-β-lactamases in Enterobacterales.
  • Tested efflux pump inhibitors CCCP, FCCP, and KCN against VIM-1-like MBLs.
  • Measured the inhibitory activity based on imipenem susceptibility in E. coli.
  • Analyzed results at varying concentrations of inhibitors.
  • Inhibitors were effective at low concentrations (0.04-19.55 µM).
  • CCCP, FCCP, and KCN restored imipenem susceptibility in E. coli.
  • The inhibitors showed novel actions against MBL enzymatic activity, suggesting dual roles.

Abstract

CCCP, FCCP and KCN exhibited inhibitory activity against VIM-1-like MBLs, restoring imipenem susceptibility in E. coli at very low concentrations (0.04-19.55 µM). Thus, certain efflux pump inhibitors, as well as the gaseous biological mediator cyanide, have a novel action as inhibitors of MBL enzymatic activity, which, in turn, renders them potentially useful as adjunct antibacterial agents.

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Cite This Study

Raro et al. (2026) studied this question.

synapsesocial.com/papers/69cf5ebc5a333a821460d451https://doi.org/10.1093/jac/dkag122
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