Holding Matthew L, Disharoon Dante, Haynes Laura M, Chakravarthy Paruchuri Bipin, Pontius M Hao Hao, Golden Krista, Shavit Jordan A, Desch Karl C, Ginsburg David, Sen Gupta Anirban, Cruz Yolanda, Drabeck Danielle H
Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, United States of America.
Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
PLoS One. 2025 Sep 19;20(9):e0332686. doi: 10.1371/journal.pone.0332686. eCollection 2025.
Interactions between predators and prey are often characterized by strong selection pressures that shape extreme physiological adaptations. Venom resistance in large-bodied South American opossums (Clade Didelphini) is a striking example, as these marsupials prey on venomous snakes and exhibit remarkable resistance to their venom. While resistance is well documented in Didelphini, relatively little is known about venom resistance in the smaller, more diverse members of Didelphidae, which inhabit the same regions and encounter the same predators. Moreover, resistance of opossum von Willebrand factor (VWF) to the venom C-type lectin-like proteins has not been previously studied under simulated vascular flow states. Here, we use microfluidic devices to investigate venom resistance in the small-bodied opossum, Monodelphis domestica, examining platelet adhesion and fibrin deposition in response to purified venom components. Additionally, we conduct platelet aggregometry and assays of serum protease inhibitors in the presence of venom from sympatric and allopatric vipers to examine patterns of species-specificity and adaptation. Our results show that M. domestica resists venom-induced disruptions to platelet function in the presence of platelet-disrupting venom components botrocetin and convulxin, while aspercetin disrupts platelet and fibrin function similarly in opossum and human samples. Whole blood aggregometry and serum protease inhibition showed patterns consistent with species-specific adaptation of mammals to their local snake venom. Unexpectedly, we find that M. domestica VWF requires increased shear force to elongate, a previously unknown aspect of opossum blood physiology that may contribute to venom resistance and may have relevance to human coagulopathies. Our findings demonstrate resistance under natural shear stress, and document venom resistance beyond large-bodied Didelphini, suggesting it is a widespread trait in South American marsupials.
捕食者与猎物之间的相互作用通常具有强大的选择压力，塑造了极端的生理适应性。大型南美负鼠（Didelphini分支）的抗毒液能力就是一个显著的例子，因为这些有袋动物以毒蛇为食，并且对其毒液表现出显著的抗性。虽然Didelphini分支的抗毒液能力已有充分记录，但对于生活在同一地区且面临相同捕食者的、体型较小且种类更多的袋鼬科成员的抗毒液能力，人们了解相对较少。此外，在模拟血管流动状态下，此前尚未研究过负鼠血管性血友病因子（VWF）对毒液C型凝集素样蛋白的抗性。在这里，我们使用微流控装置来研究小型负鼠家短尾负鼠（Monodelphis domestica）的抗毒液能力，检测其对纯化毒液成分的血小板黏附及纤维蛋白沉积情况。此外，我们在同域和异域蝰蛇毒液存在的情况下进行血小板聚集测定和血清蛋白酶抑制剂检测，以研究物种特异性和适应性模式。我们的结果表明，在家短尾负鼠存在破坏血小板功能的毒液成分蛇毒玻连蛋白和convulxin的情况下，它能抵抗毒液诱导的血小板功能破坏，而aspercetin在负鼠和人类样本中对血小板和纤维蛋白功能的破坏作用相似。全血聚集测定和血清蛋白酶抑制结果显示出与哺乳动物对当地蛇毒的物种特异性适应相一致的模式。出乎意料的是，我们发现家短尾负鼠的VWF需要增加剪切力才能伸长，这是负鼠血液生理学中一个此前未知的方面，可能有助于抗毒液能力，并且可能与人类凝血病有关。我们的研究结果证明了在自然剪切应力下的抗性，并记录了除大型Didelphini分支之外的抗毒液能力，表明这是南美有袋动物中一种广泛存在的特征。
