A protein inside our immune system could be used as a “weapon” by scientists against a common bacteria that in extreme cases is responsible for causing deadly flesh-eating disease.
Scientists in a recently published report have found that this protein helps detect and warn against the potentially lethal bacteria, Clostridium perfringens.
Dr Anukriti Mathur, lead author from John Curtin School of Medical Research (JCSMR) at the Australian National University (ANU), told The Australia Today:
“My ultimate goal is to find ways to harness the power of the immune system which can help reduce the burden of infectious diseases.”
In 2022, Dr Mathur was awarded outstanding research for her PhD thesis, “Microbial Activators of the Inflammasome”. Her research focused on understanding how the innate immune system work to recognise bacterial toxins.
She is investigating molecular mechanisms of innate immune sensing in infectious diseases and colorectal cancer.
Dr Mathur says:
“We found the bacteria produces two toxins that act in different ways and attack the body using a two-pronged approach. The first toxin punches holes into the cell surface, while the other enters the cell and damages the cell’s internal structures.”
The Clostridium perfringens bacteria, in its benign form, scientists believe is a common cause of food poisoning. However, in severe cases, it’s also responsible for causing deadly infections, including gangrene.
The authors of the study describe NLRP3’s ability to detect these toxins using the analogy of a home security system “that also doubles up as a fire detector”.
Callum Kay, from JCSMR, adds:
“We found that NLRP3 acts in a similar way; the protein can become overactive and trigger a disproportionate response that causes more harm than good and can lead to sepsis, which can be life-threatening.”
By activating a defensive response, the ANU team discovered a previously unidentified role of the NLRP3 protein to become “over-activated” and improperly respond to Clostridium perfringens infection.
Scientists say that when this happens, the body’s safety mechanisms that are designed to protect us fail, leading to potentially deadly conditions such as sepsis.
The death rate of muscle necrosis, which is caused by Clostridium perfringens, remains alarmingly high, exceeding 50 per cent, Dr Mathur observes:
“By understanding the role NLRP3 plays in detecting these deadly toxins and the defensive mechanisms it activates to protect the body, we can start to develop new techniques that target the protein and ‘dampen’ its overactive response. This would not only help prevent the body from triggering extreme and potentially deadly reactions to infection, but it could also help us find new ways to outsmart the bacteria and potentially develop new treatments.”
The ANU scientists used drugs to dampen the immune system’s defensive response triggered by NLRP3. This helped them decipher the molecular mechanisms that cause the toxins to trigger the protein’s alarm system.
According to the researchers, by better understanding these mechanisms scientists can begin to uncover ways to develop new therapies to defeat the bacteria, for which current treatment options are limited and not very effective.
In 2022, Dr Anukriti Mathur, Professor Si Ming Man, and Professor Narci Teoh were granted $65,000 by Cancer Council ACT to lead a research project investigating how a previously identified DNA sensor protects against bowel cancer, the second leading cause of cancer-related deaths.
Dr Mathur wishes to empower and mentor young girls in the field of STEM:
“I have been privileged throughout my life with mentors and colleagues who have helped me grow and develop into an independent researcher that I am today. I believe that empowering and mentoring young girls is crucial to help them garner confidence and pursue their careers in STEM. As an academic supervisor,I have always tried to support, promote and motivate the next generation women scientists.”
Dr Mathur also hopes that her work can further narrow the gap in knowledge of the immune system and lead her to establish her innate immunology-focused laboratory that would foster Australia and India collaborations.
“In my opinion, a strong partnership between the two nations has an immense potential to bring breakthroughs in the areas of Science and Technology. The establishment of the Australia-India Strategic Research Fund is a great step for creating research collaboration and opportunities between the two nations. As an Indian-Australian researcher, such funding opportunities helped us to collaborate with bright minds of both nations in our quest to tackle global problems including anti-microbial resistance.”