Resensitizing Carbapenem- and Colistin-resistant Bacteria to Antibiotics Using Auranofin

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Oct 17

PMID 33067430

Citations 49

Authors

Hongzhe Sun

Qi Zhang

Runming Wang

Haibo Wang

Yuen-Ting Wong

Minji Wang

Quan Hao

Aixin Yan

Richard Yi-Tsun Kao

Pak-Leung Ho

Hongyan Li

Affiliations

Soon will be listed here.

Abstract

Global emergence of Gram-negative bacteria carrying the plasmid-borne resistance genes, bla 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. Combination of AUR and COL rescues all mice infected by Escherichia coli co-expressing MCR-1 and New Delhi metallo-β-lactamase 5 (NDM-5). Our findings provide potential therapeutic strategy to combine AUR with antibiotics for combating superbugs co-producing MBLs and MCRs.

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