Fast standardized therapeutic-efficacy assay for drug discovery against tuberculosis.
Murine models of Mycobacterium tuberculosis infection are essential tools in drug discovery. Here we describe a fast standardized 9-day acute assay intended to measure the efficacy of drugs against M. tuberculosis growing in the lungs of immunocompetent mice. This assay is highly reproducible, allows good throughput, and was validated for drug lead optimization using isoniazid, rifampin, ethambutol, pyrazinamide, linezolid, and moxifloxacin.
Rullas
Joaquín
J
GlaxoSmithKline, Infectious Diseases Centre of Excellence in Drug Discovery, Diseases of the Developing World, Madrid, Spain.
García
Juan Ignacio
JI
Beltrán
Manuela
M
Cardona
Pere-Joan
PJ
Cáceres
Neus
N
García-Bustos
José Francisco
JF
Angulo-Barturen
Iñigo
I
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology; D004195:Disease Models, Animal; D055808:Drug Discovery; D004977:Ethambutol / Q000494:pharmacology; D024841:Fluoroquinolones; D007121:Immunocompetence; D019570:Inhalation Exposure; D007538:Isoniazid / Q000494:pharmacology; D000069349:Linezolid; D051379:Mice; D008810:Mice, Inbred C57BL; D000077266:Moxifloxacin; D023303:Oxazolidinones / Q000494:pharmacology; D011718:Pyrazinamide / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D015203:Reproducibility of Results; D012293:Rifampin / Q000494:pharmacology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology
D000081:Acetamides; D000995:Antitubercular Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D023303:Oxazolidinones; D011804:Quinolines; D011718:Pyrazinamide; D004977:Ethambutol; D000069349:Linezolid; D000077266:Moxifloxacin; D007538:Isoniazid; D012293:Rifampin