7WAA

Crystal structure of MCR-1-S treated by AgNO3

Summary for 7WAA

• Entry DOI: 10.2210/pdb7waa/pdb
• Descriptor: Probable phosphatidylethanolamine transferase Mcr-1, SILVER ION (3 entities in total)
• Functional Keywords: mcr-1-s agno3, antibiotic, transferase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 76512.44

Authors

Zhang, Q.,Wang, M.,Sun, H. (deposition date: 2021-12-13, release date: 2022-03-16, Last modification date: 2024-11-06)

Primary citation

Zhang, Q.,Wang, R.,Wang, M.,Liu, C.,Koohi-Moghadam, M.,Wang, H.,Ho, P.L.,Li, H.,Sun, H.
Re-sensitization of mcr carrying multidrug resistant bacteria to colistin by silver.
Proc.Natl.Acad.Sci.USA, 119:e2119417119-e2119417119, 2022

PubMed 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 () have become the most serious and urgent threat to healthcare. Here, we discover that silver (Ag), including silver nanoparticles, could restore colistin efficacy against -positive bacteria. We show that Ag inhibits the activity of the MCR-1 enzyme via substitution of Zn 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, Ageffectively slows down the development of higher-level resistance and reduces mutation frequency. Importantly, the combined use of Ag at a low concentration with colistin could relieve dermonecrotic lesions and reduce the bacterial load of mice infected with -1–carrying pathogens. This study depicts a mechanism of Ag inhibition of MCR enzymes and demonstrates the potentials of Ag as broad-spectrum inhibitors for the treatment of -positive bacterial infection in combination with colistin.

PubMed: 35263219
DOI: 10.1073/pnas.2119417119

Experimental method

X-RAY DIFFRACTION (1.58 Å)