Mamba venom hides a deadly second attack

Snakes have always stirred both awe and fear, but the mamba holds a special place in that story. Fast, agile, and highly venomous, it is one of Africa’s most dangerous reptiles.

A new study from the University of Queensland has revealed that mamba venom is even more insidious than previously known.

The research shows that antivenoms, while lifesaving, may only address part of the problem. By neutralizing one effect of the venom, they can reveal another hidden danger, leaving patients vulnerable to sudden and severe symptoms.

A double attack on nerves

Bryan Fry, a professor in UQ’s School of the Environment, explained how mamba venom works in surprising ways.

“The Black Mamba, Western Green Mamba and Jamesons Mamba snakes aren’t just using one form of chemical weapon, they’re launching a coordinated attack at 2 different points in the nervous system,” noted Professor Fry.

Until recently, experts thought only the Eastern Green Mamba could trigger spastic paralysis. This new research overturns that assumption, showing that three other species can also unleash both limp and spastic paralysis.

This dual action complicates treatment and may explain cases where patients initially improved, only to relapse into painful spasms.

The mystery of relapse

“This finding resolves a long-standing clinical mystery of why some patients bitten by mambas seem to initially improve with antivenom and regain muscle tone and movement only to start having painful, uncontrolled spasms,” said Professor Fry.

The venom first blocks communication between nerves and muscles, leading to weakness.

After antivenom, however, hidden toxins overstimulate the system, producing muscle spasms. “It’s like treating one disease and suddenly revealing another,” explained Professor Fry.

Mamba venom disrupts the body

The new study expands on this clinical picture by looking at the evolutionary history of mamba toxins. The researchers found that all mamba species share the same types of neurotoxins, but in different proportions.

The venom’s effects depend on how these toxins are expressed, rather than each species having unique poisons.

Spastic paralysis arises from dendrotoxins, which block potassium channels, and from fasciculins, which prevent neurotransmitter breakdown. Flaccid paralysis is driven by alpha-neurotoxins that block acetylcholine receptors at the muscles.

The combined activity produces a deadly synergy, with different toxins masking each other’s actions until antivenom changes the balance.

Geographic variation matters

PhD candidate Lee Jones, who led much of the work, emphasized the role of geography. “We also found the venom function of the mambas was different depending on their geographic location, particularly within populations of the Black Mamba from Kenya and South Africa.”

“This further complicates treatment strategies across regions because the antivenoms are not developed to counteract the intricacies of the different venoms,” said Jones.

The research confirmed that Kenyan and South African Black Mamba venoms differ in how strongly antivenoms work against them. This suggests treatment must be adapted not only to the species but also to where the snake comes from.

The evolution of venom

The toxin families themselves reveal an evolutionary puzzle. Evidence suggests that the ability to cause both flaccid and spastic paralysis arose in the last common ancestor of mambas.

Over time, species like the Eastern Green Mamba shifted toward expressing more spastic-inducing toxins, while others balanced both types.

This shows that venom evolution is not about inventing entirely new molecules but about tuning the expression of existing ones. That tuning shapes how dangerous each species appears to humans today.

Antivenoms need an upgrade

According to Professor Fry, the findings carry urgent medical weight. “This isn’t just an academic curiosity, it’s a direct call to clinicians and antivenom manufacturers.”

“By identifying the limitations of current antivenoms and understanding the full range of venom activity, we can directly inform evidence-based snakebite care. This kind of translational venom research can help doctors make better decisions in real time and ultimately saves lives.”

The study, conducted in collaboration with the Monash Venom Group, highlights a path forward. By designing antivenoms that account for both paralysis types and for regional differences, scientists hope to reduce the tens of thousands of mamba-related deaths across Africa each year.

Protecting people from mamba venom

The findings show that mamba venom is more complex than anyone expected, but science is catching up.

By understanding how the venom works in different ways and across regions, researchers can design stronger and more targeted antivenoms. This knowledge could save thousands of lives in the future and reduce the deadly toll of snakebites in Africa.

Beyond medicine, the study also highlights how evolution shaped venom into such a powerful weapon, reminding us that protecting people from mamba venom requires both scientific progress and global health attention.

The study is published in the journal Toxins.

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