Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin.

ABSTRACT: Global emergence of Gram-negative bacteria carrying the plasmid-borne resistance genes, bla_MBL and mcr, raises a significant challenge to the treatment of life-threatening infections by the antibiotics, carbapenem and colistin (COL). Here, we identify an antirheumatic drug, auranofin (AUR) as a dual inhibitor of metallo-β-lactamases (MBLs) and mobilized colistin resistance (MCRs), two resistance enzymes that have distinct structures and substrates. We demonstrate that AUR irreversibly abrogates both enzyme activity via the displacement of Zn(II) cofactors from their active sites. We further show that AUR synergizes with antibiotics on killing a broad spectrum of carbapenem and/or COL resistant bacterial strains, and slows down the development of β-lactam and COL resistance. Comb

SUBMITTER: Sun H 

PROVIDER: S-EPMC7568570 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature