Red‑on‑yellow queen: bio‑layer interferometry reveals functional diversity within Micrurus venoms and toxin resistance in prey species

Snakes in the family Elapidae largely produce venoms rich in three-fnger toxins (3FTx) that bind to the α1 subunit of nicotinic acetylcholine receptors (nAChRs), impeding ion channel activity. These neurotoxins immobilize the prey by disrupting muscle contraction. Coral snakes of the genus Micrurus are specialist predators who produce many 3FTx, making them an interesting system for examining the coevolution of these toxins and their targets in prey animals. We used a bio-layer interferometry technique to measure the binding interaction between 15 Micrurus venoms and 12 taxon-specifc mimotopes designed to resemble the orthosteric binding region of the muscular nAChR subunit. We found that Micrurus venoms vary greatly in their potency on this assay and that this variation follows phylogenetic patterns rather than previously reported patterns of venom composition. The long-tailed Micrurus tend to have greater binding to nAChR orthosteric sites than their short-tailed relatives and we conclude this is the likely ancestral state. The repeated loss of this activity may be due to the evolution of 3FTx that bind to other regions of the nAChR. We also observed variations in the potency of the venoms depending on the taxon of the target mimotope. Rather than a pattern of prey-specifcity, we found that mimotopes modeled after snake nAChRs are less susceptible to Micrurus venoms and that this resistance is partly due to a characteristic tryptophan→serine mutation within the orthosteric site in all snake mimotopes. This resistance may be part of a Red Queen arms race between coral snakes and their prey.

Biological and medical aspects related to the yellow-bellied sea snake Hydrophis platurus (Linnaeus, 1766): A view from Colombia.

In Colombia, 317 species of snakes have been recognized, of which 51 (17%) have medical importance due to the toxicity of their venom. A total of 95% of envenomations are caused by snakes of the family Viperidae and 5% of the family Elapidae. The latter form of envenomation is mainly caused by snakes of the genus Micrurus. The only sea snake described is the yellow-bellied snake (Hydrophis platurus), present in the Pacific Ocean. Although Colombia has approximately 1300 km on the Pacific coast and a significant presence of H platurus, envenomation is rare. As a result of the care of a patient with this type of envenomation and of the donation of a H platurus specimen to our laboratory, we decided to conduct this review on the most relevant biological, epidemiological and clinical aspects of this enigmatic and interesting species.

Venoms of New World Vinesnakes (Oxybelis aeneus and O. fulgidus).

Species of Oxybelis are extremely elongate arboreal snakes that are broadly distributed in the Americas, from extreme southeastern Arizona (USA) to central South America. Primarily feeding on lizards and birds, Oxybelis venoms are poorly known in general, but a prominent taxon-specific three-finger toxin (fulgimotoxin) was isolated from and is a prominent component of O. fulgidus venom; a homolog is also present in O. aeneus venom. As part of ongoing characterization of venoms from rear-fanged snakes, we describe here the composition of two broadly distributed species, O. aeneus and O. fulgidus. Venom proteomes were of very low complexity, and four protein families (LAAO, PIII SVMP, CRiSP and 3FTx) account for more than 90% of total protein composition. Venoms from both species are moderately toxic to mice and to Hemidactylus geckos, but they are nearly an order of magnitude more toxic to Anolis lizards (a native prey species). These results reflect a trend in colubrid venom composition that is becoming increasingly more common: the presence of taxon-specific toxins, specifically three-finger toxins, preferentially targeting lizards and/or birds.

Characterization of a new muscarinic toxin from the venom of the Brazilian coral snake Micrurus lemniscatus in rat hippocampus

We have isolated a new muscarinic protein (MT-Mlá) from the venom of the Brazilian coral snake Micrurus lemniscatus.The MT-Mlá was able to displace the [3H]QNB binding in the hippocampus of rats. The bindingcurve in competition experiments with MT-Mlá was indicative of two types of [3H]QNB-binding site with pKivalues of 9.08±0.67 and 6.17±0.19, n=4, suggesting that various muscarinic acetylcholine receptor(mAChR) subtypes may be the target proteins of MT-Mlá. The MT-Mlá and the M1 antagonist pirenzepinecaused a dose-dependent block on total [3H]inositol phosphate accumulation induced by carbachol. TheIC50 values for MT-Mlá and pirenzepine were, respectively, 33.1 and 2.26 nM. Taken together, these studies indicate that the MT-Mlá has antagonist effect on mAChRs in rat hippocampus.The results of the present study show, for the first time, that mAChRs function is drasticallyaffected by MT-Mlá since it not only has affinity for mAChRs but also has the ability to inhibit mAChRs.