The case for developing β-lactam drugs to treat Mycobacterium tuberculosis infections

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, kills >1 million people per year. Despite the success of β-lactam antibiotics against many Gram-positive and Gram–negative bacteria via inhibition of penicillin binding proteins (PBPs), β-lactams with broad clinical efficacy against Mtb have not been developed. In vitro studies with β-lactams against Mtb manifest promising activity, though optimization of in vivo activity is likely required. We provide an overview of the functions of Mtb enzymes potentially involved in β-lactam activity (including PBPs, Ldts, and β-lactamases), and of medicinal chemistry efforts to identify β-lactams active against Mtb. We hope that this Chapter will promote focussed efforts on PBP/Ldt inhibitors for TB treatment.