Hydroxyhexylitaconic acids as potent IMP-type metallo-β-lactamase inhibitors for controlling carbapenem resistance in Enterobacterales.

ABSTRACT: Metallo-β-lactamases (MBLs) represent one of the main causes of carbapenem resistance in the order Enterobacterales. To combat MBL-producing carbapenem-resistant Enterobacterales, the development of MBL inhibitors can restore carbapenem efficacy for such resistant bacteria. Microbial natural products are a promising source of attractive seed compounds for the development of antimicrobial agents. Here, we report that hydroxyhexylitaconic acids (HHIAs) produced by a member of the genus Aspergillus can suppress carbapenem resistance conferred by MBLs, particularly IMP (imipenemase)-type MBLs. HHIAs were found to be competitive inhibitors with micromolar orders of magnitude against IMP-1 and showed weak inhibitory activity toward VIM-2, while no inhibitory activity against

SUBMITTER: Wachino J-i 

PROVIDER: S-EPMC10913484 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature