The venom of crustaceans from underwater caves could help produce new drugs

Many animals use the venom they produce for self-defense or hunting. The components of such venom – toxins, affect various physiological processes, disrupting them. That is why they are interesting from the point of view of pharmacology. The venoms of some groups of animals – such as snakes, spiders, scorpions and insects – have already been quite well researched. However, knowledge about the venoms of marine animals is still limited, so many new discoveries are possible.

It was only a few years ago that it was discovered that there are also poisonous crustaceans – several centimeters long shovelpods (Remipedes), floating in underwater caves penetrated by sea water.

Dr. Björn von Reumont was the first to describe the production of venom by shovelpods in 2014. Currently, together with a multidisciplinary team, he conducts research at Goethe University in Frankfurt. The team consists of partners working with the Fraunhofer Institute for Translational Medicine (ITMP) within the LOEWE Center for Translational Biodiversity, as well as collaborators from the University of Leuven, Cologne, Berlin and Munich.

Scientists have managed to characterize a group of toxins produced by a worm-like shoveller Xibalbanus tulumensis. It owes its name to Mayan mythology. Xibalba is a mythical underground land of the dead, the entrance to which is said to be in cave systems on Mexico's Yucatan Peninsula.

Xibalbanus tulumensis injects its victims with venom produced in its venom gland. This toxin contains a variety of components, including a new type of peptide. Some of these peptides contain a characteristic structural element that is known from other toxins, especially those produced by spiders: several amino acids (cysteines) of the peptide are linked together in such a way that they form a knot-like structure. This in turn makes these peptides resistant to enzymes, heat and extreme pH values. Such knotty structures often act as neurotoxins, interacting with ion channels and paralyzing the victim. As studies have shown, all tested peptides, in particular Xib1, Xib2 and Xib13, effectively block potassium channels in mammalian cells. “This inhibition is extremely important when it comes to developing drugs for a number of neurological diseases, including epilepsy,” von Reumont said. The article was published in the journal “BMC Biology”.

Xib1 and Xib13 also have the ability to block voltage-gated sodium channels, such as those found in nerve or heart muscle cells. Moreover, in sensory neurons of higher mammals, both peptides can activate two proteins – PKA-II and ERK1/2 kinases – involved in signal transduction. The latter suggests that they are involved in pain sensitization, which opens up new approaches in pain therapy. – Finding appropriate candidates and comprehensive characterization of their effects, and thus laying the foundations for safe and effective drugs, is currently only possible in a large interdisciplinary team, as in the case of our study – pointed out von Reumont. Research is hampered by the fact that the shovelpod habitat is under serious threat from the construction of the Tren Maya intercity rail network that crosses the Yucatan Peninsula.

– Cenote (a type of sinkhole characteristic of limestone plains) is an extremely sensitive ecosystem – explained von Reumont, who, as an experienced cave diver, collected shovelpods in the Yucatan during several cave diving expeditions. – Our study highlights the importance of protecting biodiversity not only because of its ecological importance, but also because of the potential substances that may be of key importance to us, humans – he added.