Combination of Mycobacterium tuberculosis RS Ratio and CFU Improves the Ability of Murine Efficacy Experiments to Distinguish between Drug Treatments

Author:

Dide-Agossou Christian1ORCID,Bauman Allison A.2,Ramey Michelle E.2,Rossmassler Karen34,Al Mubarak Reem34,Pauly Samantha34,Voskuil Martin I.56,Garcia-Cremades Maria78,Savic Rada M.67910ORCID,Nahid Payam691011,Moore Camille M.12,Tasneen Rokeya13,Nuermberger Eric L.13ORCID,Robertson Gregory T.26ORCID,Walter Nicholas D.346

Affiliation:

1. Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA

2. Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, USA

3. Rocky Mountain Regional VA Medical Center, Aurora, Colorado, USA

4. Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

5. Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

6. Consortium for Applied Microbial Metrics, Aurora, Colorado, USA

7. Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA

8. Departamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain

9. Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, California, USA

10. Division of HIV, Infectious Diseases and Global Medicine, University of California San Francisco, San Francisco, California, USA

11. UCSF Center for Tuberculosis, San Francisco, California, USA

12. Division of Biostatistics and Bioinformatics, National Jewish Health, Denver, Colorado, USA

13. Center for Tuberculosis Research, Johns Hopkins University, Baltimore, Maryland, USA

Abstract

Murine tuberculosis drug efficacy studies have historically monitored bacterial burden based on CFU of Mycobacterium tuberculosis in lung homogenate. In an alternative approach, a recently described molecular pharmacodynamic marker called the RS ratio quantifies drug effect on a fundamental cellular process, ongoing rRNA synthesis.

Funder

Bill and Melinda Gates Foundation

CU | CU Anschutz | University of Colorado School of Medicine, Anschutz Medical Campus

HHS | Centers for Disease Control and Prevention

HHS | National Institutes of Health

U.S. Department of Veterans Affairs

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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