Morecroft Holly, Zdenek Christina N, Chowdhury Abhinandan, Dunstan Nathan, Hay Chris, Fry Bryan G
Adaptive Biotoxicology Lab, School of the Environment, University of Queensland, St Lucia, QLD 4072, Australia.
Australian Reptile Academy, Ripley, QLD 4306, Australia.
Toxins (Basel). 2025 Aug 18;17(8):417. doi: 10.3390/toxins17080417.
Australian elapid snakes possess potent procoagulant venoms, capable of inducing severe venom-induced consumption coagulopathy (VICC) in snakebite victims through rapid activation of the coagulation cascade by converting the FVII and prothrombin zymogens into their active forms. These venoms fall into two mechanistic categories: FXa-only venoms, which hijack host factor Va, and FXa:FVa venoms, containing a complete venom-derived prothrombinase complex. While previous studies have largely focused on human plasma, the ecological and evolutionary drivers behind prey-selective venom efficacy remain understudied. Here, thromboelastography was employed to comparatively evaluate venom coagulotoxicity across prey classes (amphibian, avian, rodent) and human plasma, using a taxonomically diverse selection of Australian snakes. The amphibian-specialist species (Red-Bellied Black Snake) exhibited significantly slower effects on rodent plasma, suggesting evolutionary refinement towards ectothermic prey. In contrast, venoms from dietary generalists retained broad efficacy across all prey types. Intriguingly, notable divergence was observed within (Eastern Brown Snake): Queensland populations of this species, and all other (brown snake) species, formed rapid but weak clots in prey and human plasma. However, the South Australian populations of produced strong, stable clots across prey plasmas and in human plasma. This is a trait shared with species (taipans) and therefore represents an evolutionary reversion towards the prothrombinase phenotype present in the and last common ancestor. Clinically, this distinction has implications for the pathophysiology of human envenomation, potentially influencing clinical progression, including variations in clinical coagulopathy tests, and antivenom effectiveness. Thus, this study provides critical insight into the ecological selection pressures shaping venom function, highlights intraspecific venom variation linked to geographic and phylogenetic divergence, and underscores the importance of prey-focused research for both evolutionary toxinology and improved clinical management of snakebite.
澳大利亚眼镜蛇科蛇类拥有强效促凝血毒液，能够通过将凝血因子VII和凝血酶原酶原转化为活性形式，快速激活凝血级联反应，从而在蛇咬伤受害者体内引发严重的毒液诱导性消耗性凝血病（VICC）。这些毒液可分为两种作用机制类型：仅产生FXa的毒液，这类毒液利用宿主的因子Va；以及FXa:FVa毒液，其含有完整的源自毒液的凝血酶原酶复合物。虽然先前的研究主要集中在人体血浆上，但猎物选择性毒液效力背后的生态和进化驱动因素仍未得到充分研究。在此，我们采用血栓弹力图法，利用分类多样的澳大利亚蛇类，比较评估不同猎物类别（两栖类、鸟类、啮齿类）和人体血浆中的毒液凝血毒性。以两栖类为食的物种（红腹黑蛇）对啮齿类血浆的作用明显较慢，这表明其在进化过程中对变温猎物进行了优化。相比之下，食性广泛的蛇类的毒液在所有猎物类型中都保持着广泛的效力。有趣的是，在东部棕蛇中观察到了显著差异：该物种的昆士兰种群以及所有其他棕蛇物种，在猎物和人体血浆中形成的凝块迅速但较弱。然而，南澳大利亚的东部棕蛇种群在所有猎物血浆和人体血浆中都产生了强大、稳定的凝块。这是太攀蛇属物种共有的特征，因此代表了向存在于太攀蛇属和棕蛇属最后共同祖先中的凝血酶原酶表型的进化逆转。在临床上，这种差异对人类中毒的病理生理学有影响，可能会影响临床进展，包括临床凝血病检测的变化以及抗蛇毒血清的有效性。因此，本研究为塑造毒液功能的生态选择压力提供了关键见解，突出了与地理和系统发育差异相关的种内毒液变异，并强调了以猎物为重点的研究对于进化毒素学和改善蛇咬伤临床管理的重要性。
