| dc.description.abstract | In Colombia, nearly 2.8% of the 4200 snakebite accidents recorded annually are inflicted by coral snakes (genus
Micrurus). Micrurus dumerilii has a broad distribution in this country, especially in densely populated areas.
The proteomic profile of its venom was here studied by a bottom-up approach combining RP-HPLC, SDS-PAGE
andMALDI-TOF/TOF. Venomproteins were assigned to eleven families, themost abundant being phospholipases
A2 (PLA2; 52.0%) and three-finger toxins (3FTx; 28.1%). This compositional profile shows thatM. dumerilii venom
belongs to the ‘PLA2-rich’ phenotype, in the recently proposed dichotomy for Micrurus venoms. Enzymatic and
toxic venom activities correlated with protein family abundances. Whole venom induced a conspicuous
myotoxic, cytotoxic and anticoagulant effect, and was mildly edematogenic and proteolytic, whereas it lacked
hemorrhagic activity. Some 3FTxs and PLA2s reproduced the lethal effect of venom. A coral snake antivenom to
Micrurus nigrocinctus demonstrated significant cross-recognition of M. dumerilii venomproteins, and accordingly,
ability to neutralize its lethal effect. The combined compositional, functional, and immunological data here reported
for M. dumerilii venom may contribute to a better understanding of these envenomings, and support
the possible use of anti-M. nigrocinctus coral snake antivenom in their treatment.
Biological significance: Coral snakes represent a highly diversified group of elapids in the NewWorld,with nearly
70 species within the genus Micrurus. Owing to their scarce yields, the biochemical composition and toxic activities
of coral snake venoms have been less well characterized than those of viperid species. In this work, an integrative
view of the venom of M. dumerilii, a medically relevant coral snake from Colombia, was obtained by a
combined proteomic, functional, and immunological approach. The venom contains proteins fromat least eleven
families, with a predominance of phospholipases A2 (PLA2), followed by three-finger toxins (3FTx). According to
its compositional profile, M. dumerilii venom can be grouped with those of several Micrurus species from North
and CentralAmerica that present a PLA2-predominant phenotype, to date it is themost southerly coral snake species
to do so. Other coral snake species that a ‘PLA2-rich’ venom, M. dumerilii venom contains both components
that form MitTx, a pain-inducing heterodimeric complex recently characterized from the venom of Micrurus
tener, also present in Micrurus mosquitensis and M. nigrocinctus venoms. In addition to a lethal three-finger
toxin, PLA2s participate in the toxicity ofM. dumerilii venom, some of them displaying ability to induce cytolysis,
muscle necrosis, and lethality to mice. An antivenom to M. nigrocinctus demonstrated significant crossrecognition
of M. dumerilii venom proteins, and accordingly, ability to neutralize its lethal effect, being of potential
therapeutic usefulness in these envenomings. | |
