Battling persistence in Tuberculosis: A tale of balanced regulation

How do these findings contribute to your research area?

We identified one reason why Mtb chronically persists in humans. Most TB patients recover from the infection without eradicating the bug from the system, leading to high relapse rates. We believe the coordinated expression of Suf and IscS systems is essential for the pathogen’s long-term persistence in the human host. Therefore, targeting both systems could be therapeutically beneficial in eradicating Mtb. Thus making them probable drug targets. Moreover, our study also suggests that without the nitric oxide signal in the host, the Suf system remains uninduced, coercing Mtb to use IscS for Fe-S biogenesis. Therefore, drugs against IscS could be beneficial for the most sensitive immune-compromised TB patients (e.g., HIV-TB coinfected individuals).

What was the exciting moment during your research?

If I recall, the most exciting moment during my research came disguised as surprising and challenging. It was the observation that we made that was the least expected and had the potential to pivot the whole direction of our story. The Mtb mutant strain I was working on was attenuated under in vitro growth conditions, which made us hypothesize that infection would be quickly cleared out of the system during a mice infection model. But, to our ultimate surprise, the IscS mutant strain became hypervirulent once inside mice post-infection. It was followed by the tedious journey of understanding the cause of this observation. This reminds me of the phrase, ‘When life gives you lemons, make a lemonade out of it.’

What do you hope to do next?

Even in the presence of drugs to treat Tuberculosis, TB remains the top pathogenic killer. The ability of Mtb to persist inside its human host and concomitantly evolve with the host is the biggest challenge in clearing TB disease from the population. Moreover, with the emergence of drug-resistant Mtb isolates, the treatment and eradication are impacted. This forces us to understand this enigmatic pathogen to be able to help cure TB. Hence, I would like to further work on Mtb and TB disease to be able to solve at least a piece of the puzzle.

Where do you seek scientific inspiration from?

Observing nature is the best way for me to seek scientific inspiration. Endless things happen every passing moment, and the curious observation of them triggering the questions ‘why’ and ‘how’ they occur is exciting. Other significant sources of inspiration are my Ph.D. mentor, Prof. Amit Singh, and my colleagues, who inspire me to keep working forward and not give up on the process. Prof. Amit urges us all to read more and more, keeping our minds open to ask the right questions to help us grow our understanding.

How do you intend to help Indian Science improve?

India is among the top nations whose population is largely affected by tuberculosis in different areas like socio-economic impact and public health. Thus, it is necessary to have the workforce to understand this pathogen and the disease, and create effective and cost-friendly drug regimens to treat and eradicate TB. As a researcher in this field, I aim to contribute to Indian science through active research and knowledge sharing, focusing on areas like drug resistance or vaccine development.