Ancient Clostridium DNA and variants of tetanus neurotoxins associated with human archaeological remains.

Ancient Clostridium DNA and variants of tetanus neurotoxins associated with human archaeological remains.
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DOI:
10.1038/s41467-023-41174-0
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发表时间:
2023-09-06
影响因子:
16.6
通讯作者:
Doxey, Andrew C.
Doxey, Andrew C.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hodgins, Harold P.;Chen, Pengsheng;Lobb, Briallen;Wei, Xin;Tremblay, Benjamin J. M.;Mansfield, Michael J.;Lee, Victoria C. Y.;Lee, Pyung-Gang;Coffin, Jeffrey;Duggan, Ana T.;Dolphin, Alexis E.;Renaud, Gabriel;Dong, Min;Doxey, Andrew C.

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对人类考古样本中微生物基因组的分析提供了古代病原体的历史快照,并为现代传染病的起源提供了见解。在这里,我们分析了来自38个人类考古样本的宏基因组数据集,并确定了与现代破伤风梭菌相关的细菌基因组序列,该梭菌产生破伤风神经毒素(TeNT)并导致疾病破伤风。这些基因组组装有不同程度的完整性,其中一部分显示出古代DNA损伤的标志。系统发育分析表明,已知的C。破伤风分支以及与C.破伤风。基因组组装编码13个具有独特取代特征的TeNT变体,包括仅在南美洲古代样本中发现的TeNT变体亚组。我们实验测试了从古代智利木乃伊样本中选择的TeNT变体,发现它在小鼠中诱导破伤风肌肉麻痹,其效力与现代TeNT相当。因此,我们的古代DNA分析鉴定出了来自神经源性C。考古人类样本中的破伤风,以及一种可导致哺乳动物疾病的TeNT新变体。对人类考古样本中微生物基因组的分析提供了古代病原体的快照。在这里,Hodgins等人分析了来自38个人类考古样本的宏基因组数据集,并确定了与现代破伤风梭菌相关的细菌基因组序列,编码破伤风神经毒素。
The analysis of microbial genomes from human archaeological samples offers a historic snapshot of ancient pathogens and provides insights into the origins of modern infectious diseases. Here, we analyze metagenomic datasets from 38 human archaeological samples and identify bacterial genomic sequences related to modern-day Clostridium tetani, which produces the tetanus neurotoxin (TeNT) and causes the disease tetanus. These genomic assemblies had varying levels of completeness, and a subset of them displayed hallmarks of ancient DNA damage. Phylogenetic analyses revealed known C. tetani clades as well as potentially new Clostridium lineages closely related to C. tetani. The genomic assemblies encode 13 TeNT variants with unique substitution profiles, including a subgroup of TeNT variants found exclusively in ancient samples from South America. We experimentally tested a TeNT variant selected from an ancient Chilean mummy sample and found that it induced tetanus muscle paralysis in mice, with potency comparable to modern TeNT. Thus, our ancient DNA analysis identifies DNA from neurotoxigenic C. tetani in archaeological human samples, and a novel variant of TeNT that can cause disease in mammals. The analysis of microbial genomes from human archaeological samples offers a snapshot of ancient pathogens. Here, Hodgins et al. analyze metagenomic datasets from 38 human archaeological samples and identify bacterial genomic sequences related to modern-day Clostridium tetani, encoding tetanus neurotoxins.
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