Journey with ‘moody’ Salmonella
We start a new series on scientists and their teams to understand not just a specific success, such as a product or publication, but how the team works on a problem, who they are and how they have dedicatedly kept the ship on course.
Salmonella–a bacterium, the same strain of which produces different diseases in different hosts, and closely related serotypes behave in starkly varied manners.
For example, Salmomella typhi is the culprit behind the life-threatening typhoid fever rampant in Africa, Asia and South America.
However, another serotype, Salmonella typhimurium, produces self-limiting localised gastroenteritis with infection restricted to the gut.
Again, the symptoms characterising the intrusion of the serotype into the body of mice starkly differ from those seen in the human body.
In mice, Salmonella typhimurium leads to a systemic disease that is analogous to human typhoid while S. typhi does not establish successful infection.
Vaccines developed against S. typhi have not resulted in lasting defence against this pathogen.
The reasons remain largely elusive. The unique behaviour of this pathogen intrigued Ayub Qadri and his team at the National Institute of Immunology (NII), New Delhi.
The Hybridoma Lab headed by Qadri has been probing the reasons for different clinical outcomes produced by these two closely related Salmonella serotypes and the mechanisms by which pathogenic Salmonella modulates the hosts’ immune defences in order to establish systemic infection.
Their aim is to understand interactions of the immune system with these closely related Salmonella serotypes, which could provide guidelines for designing a more effective vaccine – one of the areas of interest for us at the DBT and other agencies.
The Hybridoma Lab’s latest discovery is that T cells, which are primarily involved in adaptive immunity, might also contribute to innate immune responses.
Their findings also suggest that innate immune responses during microbial infections may be regulated by host lipids.
This is an important finding, and we are all keenly awaiting their further work on how these lipids may be participating in modulating innate immunity.
However, this was not a one off find. I would like to run you through the team’s relentless probe into the behaviour of Salmonella serotypes and their long journey to understand the tricky interplay between this pathogen and the host.
When Qadri started working on Salmonella typhi, any vaccine against this pathogen had not come to the market, and timely detection of the infection was very difficult.
Determined to improve this situation, he initiated an independent research programme to understand host-microbe interactions during infection by this pathogen.
In a significant finding in 2004, Qadri, with his student Amita Sharma, found that a protein called prohibitin might be engaged by S. typhi to modulate the immune system when this bacterium attacks the host (published in PNAS).
In another significant contribution a few years later, his group found that host cells produce a lipid that ‘tricks’ Salmonella into secreting flagellin ( a key bacterial molecule that generates inflammatory and innate immune responses) so that the bugs can be detected by the host sensor, triggering an immune response.
This novel finding of Ayub Qadri and Naeha Subramanium was published in Nature Immunology in 2006.
Following up on this work, Qadri’s team has now found that the ‘trick’ is detected by the bug soon after it is started and production of flagellin is stopped.
They are trying to understand the ‘trick’ so that the flagellin production can be prolonged.
In 2010, they registered another important find — that haemoglobin might be able to neutralise the anti-immune capability of Vi polysaccharide (outer coating of S. typhi responsible for its virulence; also Salmonella vaccine) and transform it into an immune activator.
They are now working on understanding how this pro-inflammatory capability of Vi might be contributing to the vaccine’s efficacy.
Led by an efficient captain, the members of his team are equally passionate. While Ajay Suresh Akhade is assessing the regulation of TLR responses, Farhat Parveen is trying to investigate the role of membrane prohibitin in cell signaling.
Sonia is probing deeper into the differences between S. typhi and S. typhimurium, and Jitender Yadav is restless to understand the modulation of the immune responses by pathogenic Salmonella.
The teams’ collective work will significantly contribute to understanding and exploiting the mechanisms of the immune system, using various tools of modern biology to pursue creative solutions to a broad range of health problems.
With inputs from science journalist Archita Bhatta