학술논문
Identification of β-Lactams Active against Mycobacterium tuberculosis by a Consortium of Pharmaceutical Companies and Academic Institutions.
Document Type
Academic Journal
Author
Gold B; Department of Microbiology & Immunology, Weill Cornell Medicine, 413 East 69th Street, New York, New York 10021, United States.; Zhang J; Department of Microbiology & Immunology, Weill Cornell Medicine, 413 East 69th Street, New York, New York 10021, United States.; Quezada LL; Department of Microbiology & Immunology, Weill Cornell Medicine, 413 East 69th Street, New York, New York 10021, United States.; Roberts J; Department of Microbiology & Immunology, Weill Cornell Medicine, 413 East 69th Street, New York, New York 10021, United States.; Ling Y; Department of Microbiology & Immunology, Weill Cornell Medicine, 413 East 69th Street, New York, New York 10021, United States.; Wood M; Department of Microbiology & Immunology, Weill Cornell Medicine, 413 East 69th Street, New York, New York 10021, United States.; Shinwari W; Department of Microbiology & Immunology, Weill Cornell Medicine, 413 East 69th Street, New York, New York 10021, United States.; Goullieux L; Sanofi, Infectious Diseases Therapeutic Area, 69280 Marcy l'Étoile, France.; Evotec (Lyon) SAS, 69007 Lyon, France.; Roubert C; Sanofi, Infectious Diseases Therapeutic Area, 69280 Marcy l'Étoile, France.; Evotec (Lyon) SAS, 69007 Lyon, France.; Fraisse L; Sanofi, Infectious Diseases Therapeutic Area, 69280 Marcy l'Étoile, France.; Bacqué E; Sanofi, Infectious Diseases Therapeutic Area, 69280 Marcy l'Étoile, France.; Evotec (Lyon) SAS, 69007 Lyon, France.; Lagrange S; Sanofi, Infectious Diseases Therapeutic Area, 69280 Marcy l'Étoile, France.; Evotec (Lyon) SAS, 69007 Lyon, France.; Filoche-Rommé B; Sanofi, Integrated Drug Discovery, 94400 Vitry sur Seine, France.; Vieth M; Lilly Biotechnology Center, Eli Lilly and Company, 10290 Campus Point Dr, San Diego, California 92121, United States.; Hipskind PA; Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, Indiana 46285, United States.; Jungheim LN; YourEncore, 20 North Meridian Street, Indianapolis, Indiana 46204, United States.; Aubé J; Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.; Scarry SM; Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.; McDonald SL; Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.; Li K; Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.; Perkowski A; Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.; Nguyen Q; Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.; Dartois V; Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, United States.; Zimmerman M; Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, United States.; Olsen DB; Merck & Co., Inc., Infectious Diseases, 770 Sumneytown Pike, West Point, Pennsylvania 19486, United States.; Young K; Merck & Co., Inc., Infectious Diseases, 770 Sumneytown Pike, West Point, Pennsylvania 19486, United States.; Bonnett S; TB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, Washington 98102, United States.; Joerss D; TB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, Washington 98102, United States.; Parish T; TB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, Washington 98102, United States.; Boshoff HI; Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Bethesda, Maryland 20892, United States.; Arora K; Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Bethesda, Maryland 20892, United States.; Barry CE 3rd; Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Bethesda, Maryland 20892, United States.; Guijarro L; Global Health Pharma R&D, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, Madrid 28760, Spain.; Anca S; Global Health Pharma R&D, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, Madrid 28760, Spain.; Rullas J; Global Health Pharma R&D, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, Madrid 28760, Spain.; Rodríguez-Salguero B; Global Health Pharma R&D, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, Madrid 28760, Spain.; Martínez-Martínez MS; Global Health Pharma R&D, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, Madrid 28760, Spain.; Porras-De Francisco E; Global Health Pharma R&D, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, Madrid 28760, Spain.; Cacho M; Global Health Pharma R&D, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, Madrid 28760, Spain.; Barros-Aguirre D; Global Health Pharma R&D, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, Madrid 28760, Spain.; Smith P; Independent Consultant, Global Health Pharma R&D, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, Madrid 28760, Spain.; Berthel SJ; Panorama Global, 2101 4th Avenue, Suite 2100, Seattle, Washington 98121, United States.; Nathan C; Department of Microbiology & Immunology, Weill Cornell Medicine, 413 East 69th Street, New York, New York 10021, United States.; Bates RH; Global Health Pharma R&D, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, Madrid 28760, Spain.
Source
Publisher: ACS Publications Country of Publication: United States NLM ID: 101654580 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2373-8227 (Electronic) Linking ISSN: 23738227 NLM ISO Abbreviation: ACS Infect Dis Subsets: MEDLINE
Subject
Language
English
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.