Modified proteins from tick saliva target root of inflammatory diseases

The bodily fluids of dangerous animals such as snakes and spiders are not ones you want to come into contact with if you can help it, but researchers continues to show how they can contain key ingredients for advanced medicines. Saliva from ticks, which spread deadly conditions such as Lyme disease, is another researchers have been studying for these reasons, and a new paper has demonstrated how proteins within it can be modified to take aim at the underlying cause of inflammatory diseases in humans.

When a tick bites a human, its secretes proteins called evasins into its saliva. These have become of great interest to scientists recently because they bind to proteins in the host's bloodstream called chemokines, which trigger an immune response characterized by the flooding of white blood cells to the injury site.

But by binding to the chemokines, the evasins effectively silence them and prevent the migration of white blood cells. This little bit of trickery is what allows the ticks to continue feeding on their host's blood without being noticed, and without causing painful inflammation. And it is this ability to avoid or minimize inflammation that has caught the scientific community's eye.

In 2017, we looked at research demonstrating how one type of evasin could be used to treat myocarditis, a potentially fatal disease in which the heart becomes dangerously inflamed. In 2020, we then saw scientists successfully synthesize the proteins from scratch, and show how they could be modified to make them more effective at binding to the chemokines.

Now, a team from Australia's Monash University is building on this with a new discovery that further shows how these proteins can be modified to better target inflammatory diseases. These include asthma, arthritis, multiple sclerosis and atherosclerosis, and all involve the body's white blood cells attacking affected tissues.

The trouble is that tick saliva contains a cocktail of evasins in order to establish a wide-ranging suppression of inflammatory response in the host. But only some of the chemokines they bind to are involved in inflammatory diseases, while others are required to maintain normal functioning of the immune system. The breakthrough here is a significant advance in figuring out how to modify the evasins so they only target chemokines that cause disease.

"We've shown that it is possible to engineer an evasin with superior ability, giving us a novel structural model by which proteins can achieve binding selectivity," said Professor Stone.

The scientists believe they have now identified the structural basis for what makes evasins recognize and bind to different chemokines. This provides the basis for engineered versions that can target pre-determined chemokines known to drive inflammatory disease, and potentially opens up an entirely new area of research.

"To date, there are no anti-inflammatory therapeutics targeting the chemokine system, which makes this work of paramount significance as it opens up a whole new avenue for anti-inflammatory research," said co-lead Dr. Ram Bhusal. "However, future work is still needed to ensure that these biomolecules avoid off-target effects."

The research was published in the journal Proceedings of the National Academy of Sciences.

Source: Monash University via MedicalXpress