Comparative venomics reveals intra, interspecific and ontogenetic changes in the venom composition of Lachesis snakes from Colombia

Background: In Colombia, Lachesis snakes are not commonly implicated in snakebite incidents. However, the considerable number of severe envenomation cases and associated mortality rates represent a significant challenge that must be overcome. A deeper comprehension of the composition of their venom, along with its variability across their distribution range, including ontogenetic and sexual variations, will contribute to the enhancement of the scarce knowledge about them and the mitigation of the consequences of snake envenomation. Methodology/Principal Findings: Through the application of snake venomics and in conjunction with biochemical characterization, here we analyze the venoms of fourteen specimens of Lachesis acrochorda (adults and juveniles) and L. muta from several geographical regions within Colombia. The venoms of juveniles and adults of L. acrochorda exhibited distinct chromatographic profiles and varying relative abundances of their toxins, indicating the presence of ontogenetic shifts, as well as enzymatic activities. Furthermore, a principal component analysis (PCA) revealed significant differences between the male and female samples in the chromatographic region associated with small peptides and nucleosides. In contrast, L. muta exhibited a relatively simple venom composition with low phospholipase activity and intense fibrinogen hydrolysis towards Aα and Bβ subunits. Finally, the Caldas sample exhibited the highest diversity of compounds and phospholipase activity. Conclusions: Overall, the results indicate that Lachesis venoms display compositional and functional variation, that depend on age, sex and geographical zone. Author summary: Snakebite envenomation represents a critical public health concern on a global scale, with tropical regions being particularly affected. However, the venoms of Lachesis snakes in Colombia remain a subject of limited scientific understanding. Although Lachesis bites are not commonly reported in the country, when they do occur, they frequently result in severe symptoms and high mortality rates. We applied detailed protein analysis methods to venom samples from fourteen juvenile and adult specimens collected across multiple regions of Colombia. Differences in the relative abundance of several venom components were found. Juveniles of Lachesis acrochorda exhibited higher levels of enzymes that break down blood proteins, while Lachesis muta venom was dominated by enzymes that promote clot formation. Furthermore, male and female venoms differed in the concentration of low molecular weight compounds. These variations could explain the range of clinical symptoms observed after envenomation, the potential impact of the effectiveness of existing antivenoms, and a deeper understanding of Lachesis venom diversity.