Title:An Extensive Review on β-lactamase Enzymes and their Inhibitors
Volume: 30
Issue: 7
Author(s): Vidhu Agarwal, Akhilesh Tiwari and Pritish Varadwaj*
Affiliation:
- Department of Applied sciences, Indian Institute of Information Technology, Allahabad, India
Keywords:
β-lactam antibiotics, β-lactamase enzymes, mutation, loops, inhibitors, kinetics.
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.
