A Novel Tool to Identify Bactericidal Compounds against Vulnerable Targets in Drug-Tolerant M. tuberculosis found in Caseum

Author:

Sarathy Jansy P.1,Xie Min1,Jones Richard M.2,Chang Adrienne3,Osiecki Paulina1,Weiner Danielle45,Tsao Wen-Shan1,Dougher Maureen1,Blanc Landry6,Fotouhi Nader7,Via Laura E.45,Barry Clifton E.48,De Vlaminck Iwijn3,Sherman David R.2,Dartois Véronique A.19ORCID

Affiliation:

1. Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA

2. Department of Microbiology, University of Washington, Seattle, Washington, USA

3. Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USA

4. Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA

5. Tuberculosis Imaging Program, Division of Intramural Research, NIAID, NIH, Bethesda, Maryland, USA

6. University of Bordeaux, CNRS, CBMN, UMR 5248, Pessac, France

7. Global Alliance for TB Drug Development, New York, New York, USA

8. Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

9. Hackensack Meridian School of Medicine, Department of Medical Sciences, Nutley, New Jersey, USA

Abstract

M. tuberculosis (Mtb) within the caseous core of necrotic granulomas and cavities is extremely drug tolerant and presents a significant hurdle to treatment success and relapse prevention. Many in vitro models of nonreplicating persistence have been developed to characterize the physiologic and metabolic adaptations of Mtb and identify compounds active against this treatment-recalcitrant population.

Funder

Bill and Melinda Gates Foundation

Division of Intramural Research, National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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