TB: Indian researchers propose new treatment regime

Indian researchers have discovered how tuberculosis bacteria can hide inside the human body and suggested new simple strategies to quickly kill the bugs in their hide-out.

The discovery, scientists say, has the potential to rewrite the standard six-month-long therapy currently followed all over the world to fight against TB – the world’s most important public health threat – as the alternative route opens up the prospect of a one-month regimen.

In the standard treatment, nearly 99% of the bugs disappear within three weeks, but the clearing of the remaining 1% takes four to six months. If one stops taking the drugs, the bacteria return with virulence.

Researchers at the Special Centre for Molecular Medicine at Jawaharlal Nehru University and All India Institute of Medical Sciences, both in Delhi, found that the bacteria hide within mesenchymal stem cells, one of the types of stem cells that differentiate into other body tissues, and stay in a dormant state without replicating.

The AIIMS-JNU team, who collaborated with academicians at International Centre for Genetic Engineering and Biotechnology, Delhi and Vanderbilt University, Tennessee, not only demonstrated the survival strategy of the bacteria but also came up with two distinct strategies to carry out surgical strikes to decimate the germs.

“The study changes the dogma of TB biology. Macrophages are historical, knows as the natural host for TB. But here we show macrophages are the natural host for active or replicating bacteria whereas mesenchymal stem cells (MSCs) are the natural host for latent or dormant TB,” Gobardhan Das, JNU professor and one of the leaders of the study team told DH.

“While treating TB majority of the organisms are cleared within three weeks of treatment, but only a few remaining bacteria do not respond to conventional antibiotics and takes an extended period of treatment. We show these organisms are hiding in an inert or dormant condition in MSCs and are not responding to antibiotics. We also show ways to kill them.”

One of the strategies is to use a lipid inhibitor like statin that makes the bugs vulnerable to common antibiotics while the other is to use medicine like rapamycin (an immunomodulator) to kill the bacteria.

“Successful treatment of TB requires the elimination of both replicating and dormant bacteria. A combination of antibiotics and inducers of autophagy (self-destruction) provides the opportunity for the successful treatment of TB,” they reported in the Journal of Clinical Investigation on Friday.

“It was earlier speculated that TB bacteria find the MSC as a very safe home to persist and do not replicate. Das and colleagues have been able to experimentally show that these MSCs serve as a natural host for the so-called persistors,” commented Seyed Hasnain, vice-chancellor of Jamia Hamdard and an acclaimed TB researcher, who is not associated with the study.

“The only caveat is that these studies have been done in the murine model and given the fact that what is true for the mouse may not necessarily be true for humans, there is a need to conduct human clinical studies to bring this otherwise excellent study to its logical conclusion that is to eliminate TB from the planet,” Hasnain told DH.