OmpV- A step towards vaccination against salmonellosis

First author interview: Dr. Deepinder Kaur was born and brought up in Patiala, Punjab. She did her bachelor’s in biotechnology from Khalsa College, Patiala, followed by masters in biotechnology from Thapar University, Patiala. She has completed her Ph.D. under the supervision of Dr. Arunika Mukhopadhaya, an Associate Professor in the Department of Biological Sciences, IISER Mohali. The title of her Ph.D. thesis is “Understanding the role of OmpV, an outer membrane protein of Salmonella Typhimurium towards bacterial pathogenesis and host immune activation.” Here she talks about her work “Salmonella Typhimurium adhesin OmpV activates host immunity to confer protection against systemic and gastrointestinal infection in mice” recently published in Infection and Immunity.

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How would you explain your paper’s key results to the non-scientific community?

Salmonellosis is a prevalent foodborne illness in developed as well as developing countries. It is a type of diarrheal disease majorly caused by the bacterium Salmonella (Salmonella Typhimurium). Children and elders are at higher risk because of their compromised immune system and it could be fatal if left untreated. To date, there is no vaccine available for salmonellosis. Only treatment available is broad spectrum of antibiotics. Because the contribution of different virulent factors (proteins) in the pathogenesis of Salmonella is still not well understood therefore, proper therapeutic targets are also not well characterized and studied yet. This leads to the emergence of multi-drug-resistant strains. Further, use of antibiotics are difficult for pregnant woman.

Figure 1. OmpV immunization leads to production of IgG and IgA antibodies that give protection against
S. Typhimurium infection

Salmonella enters the human body through contaminated food and water and then moves to the intestine to adhere to intestinal wall and colonize. After colonization, it invades the host cell and replicates. We have identified a protein on the outer-membrane of the bacterium, which is crucial for pathogenesis of the bacterium. We observed that this protein OmpV help the bacterium in adhesion to the intestinal cells. Further, we have characterized the protein in terms of its potential as vaccine candidate. We have observed that this protein OmpV can activate host immunity and induce protective responses against infection.

Our study strongly suggested that OmpV could activate both innate and adaptive immune response.

What are the possible consequences of these findings for your research area?

Our study strongly suggested that OmpV could activate both innate and adaptive immune response. It leads to the production of IgG and IgA antibodies and gives protection against S. Typhimurium infection. It is a very strong and potential candidate for vaccine development against salmonellosis. Further, the immunogenic nature of OmpV can make it good adjuvant for other vaccine formulations.

What was the exciting moment (eureka moment) during your research?

There were several eureka moments, and I enjoyed the results and the challenges as it came across during the journey. I remember texting my supervisor when I found out that OmpV is so crucial for S. Typhimurium pathogenesis. Further, I was jumping when I got the result, which hinted about integrins as a possible receptor of OmpV implying its role as an adhesin. However, I would say the experiments done on mice were the most exciting part. We immunized mice with OmpV, and they survived as compared to the non-immunized control group. These results established OmpV as a vaccine candidate and were the most satisfactory part of this study.

What do you hope to do next?

I hope that pharma companies would show more interest in employing OmpV as a candidate for making vaccine against Salmonella infection. As the continuation of my current research work, I would plan to study the role of OmpV in S. Typhi, which is the causal organism of typhoid. OmpV is also present in S. Typhi and bears 99.46 % similarity with S. Typhimurium. Currently available vaccines against typhoid do not provide a long term and more effective protection against disease. Research is still going on to develop a more efficient vaccine against typhoid, therefore, I intend to explore the role of OmpV in the protection against S. Typhi infection.

Where do you seek scientific inspiration?

Research fascinated me since my childhood. My father was working as a quality control officer in a private company in those days. He helped me to conduct few experiments for milk testing at the science fair during my secondary school. The excitement of doing an experiment and the happiness of getting a result started from there. The dream I lived with for years came true when I joined Ph.D. at IISER Mohali. It was very exciting to study the journey of survival of a small bacterium in a host with such a great defence system. I seek my inspiration from my guide Dr. Arunika Mukhopadhaya who balanced her personal and professional life so gracefully. Her training over these years not only made me a confident researcher but also a good human being.

How do you intend to help Indian science improve?

Indian science has improved immensely during the last few years. The institutes like IISERs and IITs helped to improve the scientific aptitude of undergraduate students as they are acting as a great medium of exposure to research activities. However, in my opinion, there is a need to provide a similar research environment in universities and colleges too. Therefore, if I get a chance, I would like to provide proper guidance and more research exposure to students in the universities. Moreover, I would like to inspire young minds, especially women, to pursue their careers in research and academia.

Reference

Kaur D, Gandhi S, Mukhopadhaya A. Salmonella Typhimurium adhesin OmpV activates host-immunity to confer protection against systemic and gastro-intestinal infection in mice. Infect Immun. 2021 Jun 7:IAI0012121. doi: 10.1128/IAI.00121-21.

Dr. Arunika Mukhopadhaya, Associate Professor in the Department of Biological Sciences, IISER Mohali.

Edited by: Pratibha Siwach

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