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Tuberculosis (TB) caused by Mycobacterium tuberculosis still remains one of the world’s biggest killers and kills nearly two million people every year.
Tuberculosis is hard to treat and patients often need to take multiple antibiotic drugs for as long as six months. Even then, this long treatment does not necessarily clear the infection completely because TB bugs “go to sleep” and cannot be detected using hospital diagnostic tests. These invisible bugs, known as “persisters”, can remain in human bodies for years or decadesdespite antibiotic treatments and human immune system and then reactivate to cause full-blown TB infections later in their lives. These persister bugs present a major obstacle for TB control, especially in developing countries where most TB cases are found.
To kill these persisters, one must find them first. Dr Yanmin Hu’s group has developed in vitro tuberculosis persistent models and modified the traditional mouse tuberculosis model to assess the therapeutic potential of novel TB drug regimens. Her group used resuscitation promoting factor (RPF) - a number of small protein molecules which ‘wake up’ sleeping TB bacteria and for the first time, uncovered hidden populations of persistent TB bacteria in mice. The research group found that these persisters, which are currently undetectable by conventional diagnostic methods, can be completely eradicated by TB drug regimens containing high dose rifampicin and other novel drugs. The data has major clinical implications for TB control and represents an important step in a paradigm shift to target persisters in the treatment of tuberculosis.
Hu Y, Coates AR, Mitchison DA. Sterilizing activities of fluoroquinolones against rifampin-tolerant populations of Mycobacterium tuberculosis. Antimicrobial agents and chemotherapy 2003; 47: 653-7 .
Hu Y, Liu A, Ortega-Muro F et al. High-dose rifampicin kills persisters, shortens treatment duration, and reduces relapse rate in vitro and in vivo. Front Microbiol 2015; 6: 641.
Hu Y, Pertinez H, Ortega-Muro F et al. Investigation of Elimination Rate, Persistent Subpopulation Removal, and Relapse Rates of Mycobacterium tuberculosis by Using Combinations of First-Line Drugs in a Modified Cornell Mouse Model. Antimicrobial agents and chemotherapy 2016; 60: 4778-85.
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