By studying proteins from leptospirosis-causing bacteria and the human body, researchers have identified the key pathogen-host protein interactions that are responsible for the development of the disease.
By using a wide range of advanced bioinformatics and mathematical models, the team was able to narrow down to 35 interactions between 13 bacterial and 35 human proteins that may hold potential for vaccine development. A total of 145 well-characterized proteins from the bacteria and 493 proteins from the human body were analysed to draw the conclusion.
Leptospirosis is one of the emerging zoonotic diseases and causes almost 60,000 deaths every year as there is currently no preventive vaccine for humans. The researchers studied the proteome (entire protein set) of Leptospira interrogans — the most vulnerable species — and the proteome of human beings.
Interaction network
They analysed the inter-species and intra-species protein interactions and constructed a pathogen-host interaction network which was further studied using mathematical models to identify the key interactions.
Out of the 586 pathogen-host protein interactions, 35 were identified as key interactions. “When we get an infection, the whole protein network system in our body is disturbed. We tracked the bacterial proteins and found that they are directly attacking the proteins associated with the immune system in our body,” says Swapnil ’Kumar who is first author of the paper published in Scientific Reports.
Also, two outer membrane proteins and two periplasmic proteins of the bacteria which take part in the interactions were found conserved. These proteins target human proteins involved in functions such as signal transduction, antibacterial humoral response, cell cycle and cell division. This signifies that these proteins can be explored further for effective and novel therapeutics and vaccine development.
“Validations of the findings are under way in mice model,” says Dr. Jayashankar Das, the corresponding author of the paper from the Gujarat Biotechnology Research Centre, Gandhinagar.