Nature Communications (Oct 2022)
Lysyl-tRNA synthetase, a target for urgently needed M. tuberculosis drugs
- Simon R. Green,
- Susan H. Davis,
- Sebastian Damerow,
- Curtis A. Engelhart,
- Michael Mathieson,
- Beatriz Baragaña,
- David A. Robinson,
- Jevgenia Tamjar,
- Alice Dawson,
- Fabio K. Tamaki,
- Kirsteen I. Buchanan,
- John Post,
- Karen Dowers,
- Sharon M. Shepherd,
- Chimed Jansen,
- Fabio Zuccotto,
- Ian H. Gilbert,
- Ola Epemolu,
- Jennifer Riley,
- Laste Stojanovski,
- Maria Osuna-Cabello,
- Esther Pérez-Herrán,
- María José Rebollo,
- Laura Guijarro López,
- Patricia Casado Castro,
- Isabel Camino,
- Heather C. Kim,
- James M. Bean,
- Navid Nahiyaan,
- Kyu Y. Rhee,
- Qinglan Wang,
- Vee Y. Tan,
- Helena I. M. Boshoff,
- Paul J. Converse,
- Si-Yang Li,
- Yong S. Chang,
- Nader Fotouhi,
- Anna M. Upton,
- Eric L. Nuermberger,
- Dirk Schnappinger,
- Kevin D. Read,
- Lourdes Encinas,
- Robert H. Bates,
- Paul G. Wyatt,
- Laura A. T. Cleghorn
Affiliations
- Simon R. Green
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Susan H. Davis
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Sebastian Damerow
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Curtis A. Engelhart
- Dept. of Microbiology and Immunology, Weill Cornell Medical College
- Michael Mathieson
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Beatriz Baragaña
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- David A. Robinson
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Jevgenia Tamjar
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Alice Dawson
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Fabio K. Tamaki
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Kirsteen I. Buchanan
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- John Post
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Karen Dowers
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Sharon M. Shepherd
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Chimed Jansen
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Fabio Zuccotto
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Ian H. Gilbert
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Ola Epemolu
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Jennifer Riley
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Laste Stojanovski
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Maria Osuna-Cabello
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Esther Pérez-Herrán
- Global Health Medicines R&D, GlaxoSmithKline
- María José Rebollo
- Global Health Medicines R&D, GlaxoSmithKline
- Laura Guijarro López
- Global Health Medicines R&D, GlaxoSmithKline
- Patricia Casado Castro
- Global Health Medicines R&D, GlaxoSmithKline
- Isabel Camino
- Global Health Medicines R&D, GlaxoSmithKline
- Heather C. Kim
- Dept. of Microbiology and Immunology, Weill Cornell Medical College
- James M. Bean
- Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
- Navid Nahiyaan
- Dept. of Microbiology and Immunology, Weill Cornell Medical College
- Kyu Y. Rhee
- Dept. of Microbiology and Immunology, Weill Cornell Medical College
- Qinglan Wang
- Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Vee Y. Tan
- Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Helena I. M. Boshoff
- Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Paul J. Converse
- Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, School of Medicine
- Si-Yang Li
- Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, School of Medicine
- Yong S. Chang
- Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, School of Medicine
- Nader Fotouhi
- Global Alliance for TB Drug Development
- Anna M. Upton
- Global Alliance for TB Drug Development
- Eric L. Nuermberger
- Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, School of Medicine
- Dirk Schnappinger
- Dept. of Microbiology and Immunology, Weill Cornell Medical College
- Kevin D. Read
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Lourdes Encinas
- Global Health Medicines R&D, GlaxoSmithKline
- Robert H. Bates
- Global Health Medicines R&D, GlaxoSmithKline
- Paul G. Wyatt
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- Laura A. T. Cleghorn
- Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee
- DOI
- https://doi.org/10.1038/s41467-022-33736-5
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 12
Abstract
Tuberculosis is a major cause of mortality, and the rise of drug-resistant strains of Mycobacterium tuberculosis requires the urgent development of safe and effective treatments. In this work, the authors develop a compound against lysyl-tRNA synthetase, demonstrating on-target mechanism of action and efficacy in vivo.
