β-Lactams and β-Lactamase Inhibitors: Unlocking their potential to address drug resistance

Abstract

Antibiotics such as β-lactams are one of the most widely used antibacterial drug classes in the world. The invention of the first β-lactam antibiotic (Penicillin) is regarded as a symbolic landmark in the history of modern chemotherapy. Since that time, several other β-lactam antibiotics have been added to the treatment, revolutionising the treatment of bacterial infections. Antibacterial efficacy of the β-lactams has been kept in check by the emergence of bacterial resistance. One of the most studied and common resistance mechanisms is the expression of β-lactamase enzymes. The invention of β-lactamase inhibitors which restore the efficacy of β-lactam antibiotics, has been a significant advance in the fight against microbial drug resistance. However, many recently identified β-lactamases are not inactivated by the presently available inhibitors. Despite the fact that these inhibitors may not be effective against all β-lactamases, their implementation is still welcome. This review focuses on the development of β-lactam antibiotics and the mechanism of action. It also covers the diversity of β-lactamases with an emphasis on rising bacterial resistance. It provides a summary on β-lactamase inhibitors with a focus on restoring antibiotic efficacy and the various computational approaches used in inhibitor discovery. Finally, we outlined an update on research activities aimed at discovering and developing novel β-lactamase inhibitors.