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

Abstract:

:Metallo-β-lactamases (MBLs) are a growing threat to the continued efficacy of β-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 β-lactam hydrolysis among the most clinically significant MBLs.

journal_name

ACS Infect Dis

journal_title

ACS infectious diseases

authors

Bergstrom A,Katko A,Adkins Z,Hill J,Cheng Z,Burnett M,Yang H,Aitha M,Mehaffey MR,Brodbelt JS,Tehrani KHME,Martin NI,Bonomo RA,Page RC,Tierney DL,Fast W,Wright GD,Crowder MW

doi

10.1021/acsinfecdis.7b00106

subject

Has Abstract

pub_date

2018-02-09 00:00:00

pages

135-145

issue

2

issn

2373-8227

journal_volume

4

pub_type

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