Structure and mechanism basis of β-lactam activity against Mycobacterium tuberculosis: A review of literature

Abstract

Tuberculosis (TB), caused by the infectious agent Mycobacterium tuberculosis (Mtb), has resulted in the highest mortality rates, even surpassing HIV/AIDS. The rise of Drug-resistant TB has worsened the health crisis and urgently requires new treatment approaches. The WHO has approved the repurposing of β-lactam in combination with β-lactamase (BlaC) inhibitor for treating MDR/XDR-TB. Numerous targets of β lactams present in the Mtb's cell wall are involved in its structural cytoskeleton, peptidoglycan (PG) biosynthesis. Delving into the mechanistic basis of β-lactam activity against Mtb has become a holistic approach towards developing new kinds of β-lactams and ß-lactamase-inhibitors against Mtb. This work comprehensively reviews the literature-landscape of the structure and mechanism of β-lactams binding to different PG enzymes and the β-lactamase inhibitors that can inhibit BlaC in Mtb.