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Publication Abstract from PubMed

Significance Superbugs carrying a mobile colistin resistance gene (mcr) are jeopardizing the clinical efficacy of the last-line antibiotic colistin. The development of MCR inhibitors is urgently required to cope with antibiotic-resistance emergencies. Here, we show that silver (Ag(+)) fully restores the susceptibility of mcr-1-carrying superbugs against colistin both in vitro and in vivo. We found an unprecedented tetra-silver center in the active-site pocket of MCR-1 through the substitution of the essential Zn(2+) ions in the intact enzyme, leading to the prevention of substrate binding (i.e. the dysfunction of MCR-1 in transferring phosphorylethanolamine to lipid A). Importantly, the ability of Ag(+) to suppress resistance evolution extends the lifespan of currently used antibiotics, providing a strategy to treat infections by mcr-positive bacteria.

Re-sensitization of mcr carrying multidrug resistant bacteria to colistin by silver.,Zhang Q, Wang R, Wang M, Liu C, Koohi-Moghadam M, Wang H, Ho PL, Li H, Sun H Proc Natl Acad Sci U S A. 2022 Mar 15;119(11):e2119417119. doi:, 10.1073/pnas.2119417119. Epub 2022 Mar 9. PMID:35263219^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.