An Extensive Review on β-lactamase Enzymes and their Inhibitors

Abstract

β-lactam antibiotics treat bacterial infections very effectively, but overuse and misuse have led to resistance. β-lactamase enzymes hydrolyze β-lactam antibiotics and are the primary cause of resistance in bacteria. Bacteria evolve and clinically mutate to produce such β -lactamase enzymes, which could hydrolyze newly discovered antibiotics. Therefore, carbapenems are considered to be the last resort for antimicrobial treatment. Further, different inhibitors have been discovered to fight these evolving and mutating β- lactamase enzyme resistance. These inhibitors are given in combination with the β-lactam antibiotics to treat bacterial infections effectively. But in due course of time, it has been observed that bacteria develop resistance against this combination. This is an extensive review that discusses different classes of β-lactamase enzymes, their mechanism of action, and the role of critical structural elements like loops and catalytically relevant mutations. Such mutations and structural modifications result in expanding the spectrum of activity, making these β-lactamase enzymes resistant to the newly discovered β-lactam antibiotics and their inhibitors. Detailed knowledge of such mutations, catalytically relevant structural modifications, related kinetics, and action mechanisms could help develop new inhibitors effectively. Further, a detailed discussion of available inhibitors against each class of β-lactamase enzymes is also present.

Keywords: inhibitors; kinetics; loops; mutation; β-lactam antibiotics; β-lactamase enzymes.