Research Highlight

This noxious gas aggravates TB

doi:10.1038/nindia.2020.14 Published online 29 January 2020

An international research team has discovered that the noxious gas hydrogen sulfide stimulates the growth of the TB-causing bacterium Mycobacterium tuberculosis1.

Hydrogen sulfide is a noxious gas that helps in various human pathological processes. But how this gas supports disease-causing microbes was not known till now.

The researchers found that the level of hydrogen sulfide increases following TB infection. They found that in specific cultured immune cells and TB-infected mice, reducing the levels of hydrogen sulfide gas using pharmacological agents reduced the burden of TB-causing bacterium without the use of anti-TB antibiotics. 

The findings offer new ways of treating TB. Vikram Saini, the lead author from the All India Institute of Medical Sciences in New Delhi, says patients often find it difficult to take drugs regularly in the current TB therapy, which lasts for at least 6 months. This may cause drug resistant TB. "Lowering the elevated levels of hydrogen sulfide gas could reduce the number of TB bacteria and when used with anti-TB drugs, could shorten the duration of TB treatment," Saini says.

The scientists  deciphered the molecular mechanisms and identified specific genes that TB bacteria use to overcome the toxic action of hydrogen sulfide. These genes also help the bacteria to reprogramme their metabolic processes and use the gas as a fuel to stimulate their growth. This, in turn, aggravates TB infection. 

Mice and humans use enzymes such as cystathionine β-synthase to produce hydrogen sulfide. The expression of this enzyme increases dramatically following TB infection. The scientists show that disrupting the activity of the gas-producing gene lowered the levels of this gas in mice which in turn also reduced the bacterial load and disease.

The strategy, they say, is innovative lowering the level of the gas can reduce the bacterial burden and infection in the lungs of mice without using any drugs.


References

1. Saini, V. et al. Hydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesis. Nat. Comm.(2020) doi:10.1038/s41467-019-14132-y