Re-sensitization of mcr carrying multidrug resistant bacteria to colistin by silver.

ABSTRACT: Colistin is considered the last-line antimicrobial for the treatment of multidrug-resistant gram-negative bacterial infections. The emergence and spread of superbugs carrying the mobile colistin resistance gene (mcr) have become the most serious and urgent threat to healthcare. Here, we discover that silver (Ag⁺), including silver nanoparticles, could restore colistin efficacy against mcr-positive bacteria. We show that Ag⁺ inhibits the activity of the MCR-1 enzyme via substitution of Zn²⁺ in the active site. Unexpectedly, a tetra-silver center was found in the active-site pocket of MCR-1 as revealed by the X-ray structure of the Ag-bound MCR-1, resulting in the prevention of substrate binding. Moreover, Ag⁺effectively slows down th

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC8931383 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature