Bedaquiline kills persistent Mycobacterium tuberculosis with no disease relapse: an in vivo model of a potential cure

The Journal of Antimicrobial Chemotherapy
Yanmin HuAnthony Coates

Abstract

Non-replicating persistent Mycobacterium tuberculosis is difficult to kill since the organisms become undetectable using our conventional diagnostic methods and tolerant to anti-TB drugs. Resuscitation-promoting factors (RPFs) have been used to 'wake up' non-replicating persisters, making them easy to detect. Bedaquiline is a novel bactericidal and sterilizing anti-TB drug with the potential to eradicate RPF-dependent persistent M. tuberculosis. We present the first head-to-head comparison between the standard anti-TB regimen and a bedaquiline-modified regimen in eradicating RPF-dependent persistent M. tuberculosis, using the well-defined Cornell Model. M. tuberculosis-infected mice were treated for 14 weeks with either the standard regimen (rifampicin, isoniazid, pyrazinamide and ethambutol) or the same regimen where ethambutol was replaced by bedaquiline. The efficacy of both drug regimens was measured by cfu count elimination and eradication of persistent bacteria, which was evaluated using culture filtrate (CF) containing RPFs. At the end of treatment, the remaining cfu count-negative mice were administered hydrocortisone for 8 weeks. The induced disease relapse rates were determined by the percentage of mice that became po...Continue Reading

References

Mar 1, 1966·The Journal of Experimental Medicine·R M McCuneW McDermott
Nov 1, 1994·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·L G Wayne
Jan 9, 2003·Journal of Clinical Microbiology·Albert R ZinkAndreas G Nerlich
May 25, 2004·Antimicrobial Agents and Chemotherapy·Alison K MeagherJerome J Schentag
Sep 16, 2004·The Annals of Pharmacotherapy·Ene I Ette, Paul J Williams
Feb 8, 2005·Nature Biotechnology·Denis A Mitchison
Dec 21, 2006·Antimicrobial Agents and Chemotherapy·M IbrahimN Veziris
May 15, 2007·Nature Chemical Biology·Anil KoulKoen Andries
Jul 16, 2008·The Journal of Biological Chemistry·Anil KoulKoen Andries
Jul 11, 2009·American Journal of Respiratory and Critical Care Medicine·Murad IbrahimNicolas Veziris
Oct 31, 2009·American Journal of Respiratory and Critical Care Medicine·Galina V MukamolovaMichael R Barer
Jun 11, 2011·American Journal of Respiratory and Critical Care Medicine·Tianyu ZhangEric L Nuermberger
Feb 23, 2013·JAMA : the Journal of the American Medical Association·Jerry Avorn
Mar 15, 2014·Euro Surveillance : Bulletin Européen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin·G de VriesUNKNOWN Tuberculosis in European Union Big Cities Working Group
Aug 21, 2014·The New England Journal of Medicine·Edward Cox, Katherine Laessig
Aug 21, 2014·The New England Journal of Medicine·Andreas H DiaconUNKNOWN TMC207-C208 Study Group
Sep 10, 2014·The New England Journal of Medicine·Stephen H GillespieUNKNOWN REMoxTB Consortium
Oct 23, 2014·The New England Journal of Medicine·Amina JindaniUNKNOWN RIFAQUIN Trial Team
Jan 27, 2015·American Journal of Respiratory and Critical Care Medicine·Andreas H DiaconCarl M Mendel
Jul 9, 2016·American Journal of Respiratory and Critical Care Medicine·Melissa D ChengalroyenBavesh D Kana
Jul 28, 2016·Tuberculosis·S LipworthS H Gillespie

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Citations

Dec 19, 2019·Expert Review of Anti-infective Therapy·Anthony R M CoatesPamela Yey
Oct 6, 2020·Frontiers in Immunology·Sam AfkhamiZhou Xing
Jun 26, 2020·Science Translational Medicine·Sarah M SchraderCarl Nathan
Sep 1, 2020·Current Opinion in Microbiology·Ana L MoldoveanuSophie Helaine
Nov 13, 2020·Microbiology and Molecular Biology Reviews : MMBR·Niilo KaldaluTanel Tenson
Aug 12, 2020·Antimicrobial Agents and Chemotherapy·Susanna CommandeurWilbert Bitter
Jan 21, 2021·Antimicrobial Agents and Chemotherapy·Mehak Zahoor Khan, Vinay Kumar Nandicoori
Apr 3, 2021·Frontiers in Cellular and Infection Microbiology·Hee-Jeong YangLaura E Via
Aug 7, 2021·FEMS Microbiology Reviews·J UrbaniecJ McFadden

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