Probing the Interaction of Aspergillomarasmine A with Metallo-?-lactamases NDM-1, VIM-2, and IMP-7.

ABSTRACT: Metallo-?-lactamases (MBLs) are a growing threat to the continued efficacy of ?-lactam antibiotics. Recently, aspergillomarasmine A (AMA) was identified as an MBL inhibitor, but the mode of inhibition was not fully characterized. Equilibrium dialysis and metal analysis studies revealed that 2 equiv of AMA effectively removes 1 equiv of Zn(II) from MBLs NDM-1, VIM-2, and IMP-7 when the MBL is at micromolar concentrations. Conversely, 1H NMR studies revealed that 2 equiv of AMA remove 2 equiv of Co(II) from Co(II)-substituted NDM-1, VIM-2, and IMP-7 when the MBL/AMA are at millimolar concentrations. Our findings reveal that AMA inhibits the MBLs by removal of the active site metal ions required for ?-lactam hydrolysis among the most clinically significant MBLs.

SUBMITTER: Bergstrom A 

PROVIDER: S-EPMC5807211 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature