Identification of β-Lactams Active against Mycobacterium tuberculosis by a Consortium of Pharmaceutical Companies and Academic Institutions

Rising antimicrobial resistance challenges our ability to combat bacterial infections. The problem is acute for tuberculosis (TB), the leading cause of death from infection before COVID-19. Here, we developed a framework for multiple pharmaceutical companies to share proprietary information and compounds with multiple laboratories in the academic and government sectors for a broad examination of the ability of beta-lactams to kill Mycobacterium tuberculosis (Mtb). In the TB Drug Accelerator (TBDA), a consortium organized by the Bill & Melinda Gates Foundation, individual pharmaceutical companies collaborate with academic screening laboratories. We developed a higher order consortium within the TBDA in which four pharmaceutical companies (GlaxoSmithKline, Sanofi, MSD, and Lilly) collectively collaborated with screeners at Weill Cornell Medicine, the Infectious Disease Research Institute (IDRI), and the National Institute of Allergy and Infectious Diseases (NIAID), pharmacologists at Rutgers University, and medicinal chemists at the University of North Carolina to screen similar to 8900 beta-lactams, predominantly cephalosporins, and characterize active compounds. In a striking contrast to historical expectation, 18% of beta-lactams screened were active against Mtb, many without a beta-lactamase inhibitor. One potent cephaloporin was active in Mtb-infected mice. The steps outlined here can serve as a blueprint for multiparty, intra- and intersector collaboration in the development of anti-infective agents.

Automated summary

The rising antimicrobial resistance poses challenges to combating bacterial infections. In this study, a framework was developed for pharmaceutical companies to share proprietary information and compounds with academic and government laboratories to evaluate the ability of beta-lactams in killing Mycobacterium tuberculosis. Contrary to expectations, a significant number of beta-lactams displayed activity against Mtb, with one particularly potent cephalosporin showing activity in Mtb-infected mice. The steps outlined in this study can serve as a blueprint for multi-party collaboration in the development of anti-infective agents.