TB fight gets boost with new bug breakthrough

Indian researchers have discovered how tuberculosis bacteria hide inside the human body and suggested new strategies to kill the bugs quickly.

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

In the standard treatment, nearly 99% of the bugs disappear within three weeks, but 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 (JNU) and AIIMS, 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 decimate the germs.

“The study changes the dogma of TB biology,” Gobardhan Das, JNU professor and one of the leaders of the study team, told DH.

“Macrophages are historically known 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.”

Das said in TB treatment “majority of the organisms are cleared within three weeks of treatment”, with only a few remaining bacteria not responding to conventional antibiotics and taking 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 the ways to kill them,” he said.

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 a medicine like rapamycin (an immunomodulator) to kill the bacteria.

“Successful treatment of TB requires 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.

Seyed Hasnain, Vice Chancellor of Jamia Hamdard and an acclaimed TB researcher, termed the study “excellent”.

“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,” said Hasnain, 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.