Open AccessRe-sensitization of mcr carrying multidrug resistant bacteria to colistin by silver
Author(s) -
Qi Zhang,
Runming Wang,
Minji Wang,
Chunjiao Liu,
Mohamad KoohiMoghadam,
Haibo Wang,
Pak-Leung Ho,
Hongyan Li,
Hongzhe Sun
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2119417119
Subject(s) - colistin , antimicrobial , microbiology and biotechnology , bacteria , multiple drug resistance , escherichia coli , enzyme , antibiotics , antibiotic resistance , biology , chemistry , gene , biochemistry , genetics
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 ofmcr-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 Zn2+ 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 bymcr -positive bacteria.