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

Abstract

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.