1. Identification of β-Lactams Active against Mycobacterium tuberculosis by a Consortium of Pharmaceutical Companies and Academic Institutions
- Author
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Ben Gold, Jun Zhang, Landys Lopez Quezada, Julia Roberts, Yan Ling, Madeleine Wood, Wasima Shinwari, Laurent Goullieux, Christine Roubert, Laurent Fraisse, Eric Bacqué, Sophie Lagrange, Bruno Filoche-Rommé, Michal Vieth, Philip A. Hipskind, Louis N. Jungheim, Jeffrey Aubé, Sarah M. Scarry, Stacey L. McDonald, Kelin Li, Andrew Perkowski, Quyen Nguyen, Véronique Dartois, Matthew Zimmerman, David B. Olsen, Katherine Young, Shilah Bonnett, Douglas Joerss, Tanya Parish, Helena I. Boshoff, Kriti Arora, Clifton E. Barry, Laura Guijarro, Sara Anca, Joaquín Rullas, Beatriz Rodríguez-Salguero, Maria S. Martínez-Martínez, Esther Porras-De Francisco, Monica Cacho, David Barros-Aguirre, Paul Smith, Steven J. Berthel, Carl Nathan, and Robert H. Bates
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Infectious Diseases - Abstract
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 β-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 ∼8900 β-lactams, predominantly cephalosporins, and characterize active compounds. In a striking contrast to historical expectation, 18% of β-lactams screened were active against Mtb, many without a β-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.
- Published
- 2022
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