Borja Miguel, Castañeda-Gaytán Gamaliel, Alagón Alejandro, Strickland Jason L, Parkinson Christopher L, Gutiérrez-Martínez Areli, Rodriguez-López Bruno, Zarzosa Vanessa, Lomonte Bruno, Saviola Anthony J, Fernández Julián, Smith Cara F, Hansen Kirk C, Pérez-Robles Armando, Castañeda-Pérez Sebastián, Hirst Samuel R, Olvera-Rodríguez Felipe, Fernández-Badillo Leonardo, Sigala Jesús, Jones Jason, Montaño-Ruvalcaba Carlos, Ramírez-Chaparro Ricardo, Margres Mark J, Acosta-Campaña Gerardo, Neri-Castro Edgar
Facultad de Ciencias Biológicas, Universidad Juárez del Estado de Durango, Av. Universidad s/n. Fracc. Filadelfia, C.P. 35010 Gómez Palacio, Dgo., Mexico.
Instituto de Biotecnología, Universidad Nacional Autónoma de México, Avenida Universidad 2001, Chamilpa, C.P. 62210 Cuernavaca, Mor., Mexico.
Comp Biochem Physiol C Toxicol Pharmacol. 2025 Apr;290:110129. doi: 10.1016/j.cbpc.2025.110129. Epub 2025 Jan 30.
The Crotalus molossus complex consists of five to seven phylogenetically related lineages of black-tailed rattlesnakes widely distributed in Mexico. While previous studies have noted venom variation within specific lineages of the Crotalus molossus complex, a comprehensive characterization of interspecific and ontogenetic venom variations, their functional implications, and the neutralizing ability of the Mexican antivenom against these variants remains largely unexamined. Herein, using two proteomic approaches for five lineages (C. basiliscus, C. m. molossus, C. m. nigrescens, C. m. oaxacus, and C. ornatus) of the C. molossus complex we characterized the number of toxins and their relative abundance in the venom of individuals of varying sizes. All five lineages undergo ontogenetic venom composition shifts associated with snake length. However, the pattern of ontogenetic shifts varied among lineages. In some lineages, these shifts led to significant differences in proteolytic, phospholipase A and fibrinogenolytic activities. Venom in smaller C. basiliscus, C. m. nigrescens, and C. m. oaxacus individuals had lower LD values (more lethal) in mice. Whereas the venom lethality of C. m. nigrescens (both juvenile and adult) and C. m. oaxacus (adult) was several times higher in a mammalian (mouse) model than in a reptilian (iguana) model. Antivipmyn® showed different neutralizing potencies toward venom pools. Overall, our results indicated that even among closely related rattlesnake lineages, venom phenotypes may vary greatly, impacting their function and the efficacy of antivenom neutralization.
黑尾响尾蛇复合体（Crotalus molossus complex）由五到七个系统发育相关的谱系组成，广泛分布于墨西哥。虽然先前的研究已经注意到黑尾响尾蛇复合体特定谱系内的毒液差异，但种间和个体发育过程中的毒液差异、它们的功能意义以及墨西哥抗蛇毒血清对这些变体的中和能力的全面表征在很大程度上仍未得到研究。在此，我们使用两种蛋白质组学方法对黑尾响尾蛇复合体的五个谱系（巴氏响尾蛇（C. basiliscus）、墨西哥黑尾响尾蛇指名亚种（C. m. molossus）、墨西哥黑尾响尾蛇黑化亚种（C. m. nigrescens）、墨西哥黑尾响尾蛇瓦哈卡亚种（C. m. oaxacus）和华丽响尾蛇（C. ornatus））进行研究，以表征不同大小个体毒液中的毒素数量及其相对丰度。所有五个谱系的毒液成分都会随着蛇的长度发生个体发育变化。然而，个体发育变化的模式在不同谱系之间有所不同。在一些谱系中，这些变化导致蛋白水解、磷脂酶A和纤维蛋白溶解活性存在显著差异。较小的巴氏响尾蛇、墨西哥黑尾响尾蛇黑化亚种和墨西哥黑尾响尾蛇瓦哈卡亚种个体的毒液在小鼠中的LD值较低（毒性更强）。而墨西哥黑尾响尾蛇黑化亚种（幼体和成体）和墨西哥黑尾响尾蛇瓦哈卡亚种（成体）的毒液在哺乳动物（小鼠）模型中的致死性比在爬行动物（鬣蜥）模型中高几倍。抗蝰蛇毒血清（Antivipmyn®）对毒液池显示出不同的中和效力。总体而言，我们的结果表明，即使在亲缘关系密切的响尾蛇谱系中，毒液表型也可能有很大差异，从而影响其功能和抗蛇毒血清中和的效果。
