Comparative gender peptidomics of Bothrops atrox venoms: are there differences between them?

Abstract Background: Bothrops atrox is known to be the pit viper responsible for most snakebites and human fatalities in the Amazon region. It can be found in a wide geographical area including northern South America, the east of Andes and the Amazon basin. Possibly, due to its wide distribution and generalist feeding, intraspecific venom variation was reported by previous proteomics studies. Sex-based and ontogenetic variations on venom compositions of Bothrops snakes were also subject of proteomic and peptidomic analysis. However, the venom peptidome of B. atrox remains unknown. Methods: We conducted a mass spectrometry-based analysis of the venom peptides of individual male and female specimens combining bottom-up and top-down approaches. Results: We identified in B. atrox a total of 105 native peptides in the mass range of 0.4 to 13.9 kDa. Quantitative analysis showed that phospholipase A2 and bradykinin potentiating peptides were the most abundant peptide families in both genders, whereas disintegrin levels were significantly increased in the venoms of females. Known peptides processed at non-canonical sites and new peptides as the Ba1a, which contains the SVMP BATXSVMPII1 catalytic site, were also revealed in this work. Conclusion: The venom peptidomes of male and female specimens of B. atrox were analyzed by mass spectrometry-based approaches in this work. The study points to differences in disintegrin levels in the venoms of females that may result in distinct pathophysiology of envenomation. Further research is required to explore the potential biological implications of this finding.

摘要：背景：Bothrops atrox 被认为是亚马逊地区导致大多数蛇咬和人类死亡事件的土著蝰蛇。其分布范围广泛，包括南美洲北部、安第斯山脉东部以及亚马逊盆地。可能由于分布广泛且食性杂食，既往的蛋白质组学研究报道了其种内毒液变异。针对 Bothrops 蛇毒液组成的性别和发育阶段变异也已成为蛋白质组和肽组分析的研究主题。然而，B. atrox 的毒液肽组尚属未知。方法：本研究采用基于质谱分析的方法，结合自下而上和自上而下的策略，对个体雌雄样本的毒液肽进行了分析。结果：在 B. atrox 中，我们鉴定出质量范围为 0.4 至 13.9 kDa 的 105 种原生肽。定量分析表明，磷脂酶 A2 和缓激肽增强肽在雌雄两性中均为最丰富的肽家族，而溶血素水平在雌性毒液中显著升高。此外，本研究还揭示了在非典型位点处理过的已知肽以及新发现的 Ba1a 肽（包含 SVMP BATXSVMPII1 催化位点）的存在。结论：本研究通过基于质谱的方法分析了 B. atrox 雌雄样本的毒液肽组。研究指出，雌性毒液中的溶血素水平差异可能导致中毒后不同的病理生理学变化。为进一步探索该发现的潜在生物学意义，尚需进一步研究。