Antibiotics are drugs that destroy or prevent the growth of bacteria. When antibiotics are used improperly or in excess, bacteria can mutate and become resistant to them, rendering an otherwise effective antibiotic ineffective. Commona bacterial infections are usually treated with beta-lactam antibiotics such as cephalosporins or carbapenems. However, in recent years, some bacteria have developed resistance factors called metallo-β-lactamases (MBLs), which hydrolyze almost all commonly used β-lactam antibiotics, rendering them clinically ineffective. As a result, since the mid-1990s, Colistin (COL), the so-called “last line of defense”, has been used to treat these infections caused by drug-resistant bacteria. Unfortunately, in 2015, scientists and clinicians identified a completely new resistance factor that is capable of rendering colistin ineffective - mobile colistin resistance (MCR). This resistance enzyme has a very different structure and biological function from MBLs, and therefore there is currently no effective and universal treatment strategy for multidrug-resistant superbug infections with both MCR and MBLs in clinical practice. Therefore, it is an urgent problem for scientists and clinicians to find an economical and effective alternative therapy with few side effects.


      Auranofin (AUR), an antirheumatic gold-based drug, was discovered by a domestic group to be able to act as a co-inhibitor of MBL and MCR, and to restore the antibacterial viability of carbapenem antibiotics (e.g., meropenem meropenem, MER) and mucins against MCR-producing and MBL-producing multi-resistant superbugs at the same time. bacteria with multidrug-resistant MCR- and MBL-producing superbugs. Detailed studies revealed that AUR was able to displace zinc ions from the active center of the MBL enzyme by binding to the crucial cysteine in its active center, forming a gold-bound MBL protein, thus completely disabling its ability to hydrolyze antibiotics; at the same time, AUR was able to efficiently attack phosphorylated tyrosines/histidines in the MCR enzyme and occupy the active site, resulting in a blockage of the transfer of phosphatidylethanolamine, and the loss of its biological function against Mucor. The AUR can effectively attack the phosphorylated tyrosine/histidine in MCR enzyme and occupy the active site, thus blocking its ability to transfer ethanolamine phosphate, thus depriving it of the ability to fight against mucin.