Digesting DNA To Save Limbs From Snakebite

Treating mice with a DNA-digesting enzyme after a snakebite could prevent the destruction of tissue caused by saw-scaled viper venom.

AsianScientist (Apr. 27, 2016) – Researchers from India have identified what makes the venom from the saw-scaled viper (Echis carinatus) so destructive: the involvement of cells known as neutrophils. Their findings, published in Nature Communications, could lead to therapies to prevent the devastating tissue damage and amputation that often results from snakebites.

Every year, 5.5 million people are bitten by snakes, resulting in some 125,000 deaths. The small but aggressive saw-scaled viper is one of the top four venomous snakes in India, where 50,000 people are estimated to die of snakebite each year. Apart from death, the venom of the saw-scaled viper is well known for causing extensive tissue damage, often requiring amputation.

In an attempt to understand the mechanism of venom-induced tissue destruction, a team led by Professor Kempaiah Kemparaju from the University of Mysore studied the effect of the venom on various immune cells.

“Initially, we suspected that macrophages played a key role and intended to find out the effect of E. carinatus venom on macrophage differentiation into M1 and M2 subtypes,” Kemparaju explained. “However, the macrophage isolation protocol invariably results in isolation of neutrophils as well. Since neutrophils were available in plenty, out of curiosity, we also tested the effect of venom on neutrophils.”

The decision to study neutrophils proved to be serendipitous. Kemparaju and his team found that saw-scale viper venom not only caused the neutrophils to die but also induced the release of neutrophil extracellular traps (NETs), a sticky web of DNA designed to prevent the spread of bacteria.

“When we started digging for more information on neutrophils, we found out that several pathogenic bacteria were able to degrade NETs-DNA by secreting the enzyme DNase, using this as an efficient strategy to escape from the NETs and reach the blood circulation,” Kemparaju said.

Interestingly, they found that saw-scaled viper venom lacked DNase activity, unlike cobra venom which is highly lethal and neurotoxic.

“This finding led us to reason that E. carinatus venom will induce massive NETs formation, not only blocking the blood vessels but also trapping venom toxins at the bite site. Eventually, the tissue suffers from starvation due to a lack of blood supply, and in addition, the trapped venom toxins (especially extracellular matrix degrading enzymes) degrade the tissue in its vicinity,” he added.

Working in mice, the team found that tail vein injection of the venom did not lead to tissue damage if the mice lacked neutrophils. Similarly, when the venom was co-injected with DNase, tissue damage was greatly reduced, although the mice also died faster. The researchers hypothesize that the lack of NETs allowed the saw-scaled viper venom to behave more like cobra venom, rapidly entering the circulation and leading to lethal systemic toxicity.

“Our results suggest that even if you administer DNase three hours after E. carinatus venom injection or a natural bite, you can prevent the loss of limb. However, co-injection of DNase with venom was highly fatal. Delayed administration of DNase enzyme, on the other hand, was not fatal and prevents tissue damage 100 percent,” Kemparaju said.

The team next plans to find out more about the molecular mechanisms underlying tissue damage caused by other types of vipers and colubrid snakes, as well as chronic conditions such as diabetic gangrene.


The article can be found at: Katkar et al. (2016) NETosis and Lack of DNase Activity are Key Factors in Echis carinatus Venom-Induced Tissue Destruction.

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Copyright: Asian Scientist Magazine; Photo: Kempaiah Kemparaju/University of Mysore.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Rebecca did her PhD at the National University of Singapore where she studied how macrophages integrate multiple signals from the toll-like receptor system. She was formerly the editor-in-chief of Asian Scientist Magazine.

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