Abstract
Multidrug bacterial resistance endangers clinically effective antimicrobial therapy and continues to cause major public health problems, which have been upgraded to unprecedented levels in recent years, worldwide. β-Lactam antibiotics have become an important weapon to fight against pathogen infections due to their broad spectrum. Unfortunately, the emergence of antibiotic resistance genes (ARGs) has severely astricted the application of β-lactam antibiotics. Of these, New Delhi metallo-β-lactamase-1 (NDM-1) represents the most disturbing development due to its substrate promiscuity, the appearance of variants, and transferability. Given the clinical correlation of β-lactam antibiotics and NDM-1-mediated resistance, the discovery, and development of combination drugs, including NDM-1 inhibitors, for NDM-1 bacterial infections, seems particularly attractive and urgent. This review summarizes the research related to the development and optimization of effective NDM-1 inhibitors. The detailed generalization of crystal structure, enzyme activity center and catalytic mechanism, variants and global distribution, mechanism of action of existing inhibitors, and the development of scaffolds provides a reference for finding potential clinically effective NDM-1 inhibitors against drug-resistant bacteria.
Highlights
Abusing the use of antibiotics causes the mass production of resistant bacteria and resistance genes
Resistant bacteria and resistance genes can be transmitted to humans via the food chain and environments, which leads to a variety of infectious illnesses, including norovirus and hepatitis A [1,2,3]
A large number of studies have shown that multidrug-resistant bacteria (MDR) mainly focuses on gramnegative bacteria, especially carbapenem-resistant Enterobacteriaceae (CRE) and carbapenemresistant Acinetobacter baumannii (CRAB) [6,7]
Summary
Abusing the use of antibiotics causes the mass production of resistant bacteria and resistance genes. Bacteria have developed sophisticated resistance mechanisms to resist treatments with β-lactam antibiotics. Class B BLs, known as metallo β-lactamases (MBLs) (such as IMP, VIM, NDM), catalyze the hydrolysis of β-lactam antibiotics through a non-covalent mechanism and are characterized by one or two equivalents of bound zinc (Zn) ions that are indispensable for enzyme activity [17,18]. The most effective method against NDM-1 is to design an inhibitor to protect β-lactam drugs from enzyme hydrolysis. The major advances in NDM-1 inhibitor discovery and development were presented This summary focuses on the effective structural basis and inhibitory mechanism of inhibitors and inhibitors that synergize with β-lactam antibiotics to restore the drug sensitivity of clinically relevant NDM-1-expressing bacteria in vitro and in vivo
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
