New Delhi metallo-β-lactamase-1 inhibitors for combating antibiotic drug resistance: recent developments

Abstract

The most common mechanism of the resistance to β-lactam antibiotics is the expIdentification of cisplatin and palladiuression of β-lactamases, which can hydrolyze the β-lactam moiety and deactivate these antimicrobials. The worldwide prevalence of New Delhi metallo-β-lactamase-1 (NDM-1), also known as carbapenemase has created distress among clinicians. NDM-1 is a type of metallo β-lactamase (type of β-lactamases which require metal ions for their catalytic action) produced in pathogens carrying blaNDM-1 gene. These NDM-1 producing pathogens are resistant to all β-lactam antibiotics including carbapenems and are greatest threat to public health as they can easily extend via horizontal gene transfer. Various NDM-1 variants have been evolved over time and it may further evolve in the future due to several factors such as bacterial gene mutation and overuse of antibiotics. In the past 10 years, various NDM-1 inhibitors have been reported showing diverse chemical structure. In spite of a great development in terms of structural and mechanistic information, the design of a potent inhibitor of NDM-1 to be approved clinically remains challenging, this could be due to structural complexity of the enzyme that limits the development of clinically useful NDM-1 inhibitors. Along with designing of novel and effective NDM-1 inhibitors, measures should be taken for controlling multidrug resistance. Currently, there is non-availability of NDM-1 inhibitors clinically therefore clinicians are facing a huge challenge in treating infections due to multidrug-resistant bacteria. This review article has been planned to discuss about antibiotic resistance, NDM-1, mechanism of antibiotic resistance by NDM-1, and recent updates in the development of NDM-1 inhibitors as well as mechanism of action of NDM-1 inhibitors.