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是什么导致了卡尔·帕特森·施密特的死亡?南非绿树蟒(青环蛇)的毒液腺转录组学、毒液学和抗毒液学综合分析。

What killed Karl Patterson Schmidt? Combined venom gland transcriptomic, venomic and antivenomic analysis of the South African green tree snake (the boomslang), Dispholidus typus.

机构信息

Laboratorio de Venómica Estructural y Funcional, Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain.

Alistair Reid Venom Research Unit, Parasitology Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

出版信息

Biochim Biophys Acta Gen Subj. 2017 Apr;1861(4):814-823. doi: 10.1016/j.bbagen.2017.01.020. Epub 2017 Jan 24.

Abstract

BACKGROUND

Non-front-fanged colubroid snakes comprise about two-thirds of extant ophidian species. The medical significance of the majority of these snakes is unknown, but at least five species have caused life-threatening or fatal human envenomings. However, the venoms of only a small number of species have been explored.

METHODS

A combined venomic and venom gland transcriptomic approach was employed to characterise of venom of Dispholidus typus (boomslang), the snake that caused the tragic death of Professor Karl Patterson Schmidt. The ability of CroFab™ antivenom to immunocapture boomslang venom proteins was investigated using antivenomics.

RESULTS

Transcriptomic-assisted proteomic analysis identified venom proteins belonging to seven protein families: three-finger toxin (3FTx); phospholipase A (PLA); cysteine-rich secretory proteins (CRISP); snake venom (SV) serine proteinase (SP); C-type lectin-like (CTL); SV metalloproteinases (SVMPs); and disintegrin-like/cysteine-rich (DC) proteolytic fragments. CroFab™ antivenom efficiently immunodepleted some boomslang SVMPs.

CONCLUSIONS

The present work is the first to address the overall proteomic profile of D. typus venom. This study allowed us to correlate the toxin composition with the toxic activities of the venom. The antivenomic analysis suggested that the antivenom available at the time of the unfortunate accident could have exhibited at least some immunoreactivity against the boomslang SVMPs responsible for the disseminated intravascular coagulation syndrome that caused K.P. Schmidt's fatal outcome.

GENERAL SIGNIFICANCE

This study may stimulate further research on other non-front-fanged colubroid snake venoms capable of causing life-threatening envenomings to humans, which in turn should contribute to prevent fatal human accidents, such as that unfortunately suffered by K.P. Schmidt.

摘要

背景

非前齿类游蛇约占现存蛇类物种的三分之二。这些蛇的大多数医学意义尚不清楚,但至少有五个物种已导致危及生命或致命的人类中毒。然而,只有少数几种蛇毒得到了探索。

方法

采用毒液组学和毒液腺转录组学相结合的方法,对导致 Karl Patterson Schmidt 教授悲惨死亡的 Dispholidus typus(巨环扁尾海蛇)蛇的毒液进行了特征描述。使用抗蛇毒血清组学研究了 CroFab™抗蛇毒血清对巨环扁尾海蛇毒液蛋白的免疫捕获能力。

结果

基于转录组的蛋白质组学分析鉴定出属于七个蛋白家族的毒液蛋白:三指毒素(3FTx);磷脂酶 A(PLA);富含半胱氨酸的分泌蛋白(CRISP);蛇毒丝氨酸蛋白酶(SVSP);C 型凝集素样(CTL);SV 金属蛋白酶(SVMP);和整联蛋白样/富含半胱氨酸(DC)蛋白水解片段。CroFab™抗蛇毒血清有效地免疫耗尽了一些巨环扁尾海蛇 SVMP。

结论

本研究首次针对 D. typus 毒液的整体蛋白质组图谱进行了研究。这项研究使我们能够将毒素组成与毒液的毒性活性相关联。抗蛇毒血清组学分析表明,在不幸发生事故时可使用的抗蛇毒血清可能至少对引起 K.P. Schmidt 致命后果的弥散性血管内凝血综合征的巨环扁尾海蛇 SVMP 具有一定的免疫反应性。

一般意义

这项研究可能会激发对其他能够引起危及生命的人类中毒的非前齿类游蛇毒液的进一步研究,从而有助于防止像 K.P. Schmidt 那样不幸的人类致命事故的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f3/5335903/06bd4734350e/gr1.jpg

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