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

Harold P. Hodgins, Pengsheng Chen, Briallen Lobb, Xin Wei, Benjamin J.M. Tremblay, Michael J. Mansfield, Victoria C.Y. Lee, Pyung Gang Lee, Jeffrey Coffin, Ana T. Duggan, Alexis E. Dolphin, Gabriel Renaud*, Min Dong*, Andrew C. Doxey*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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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.

Original languageEnglish
Article number5475
JournalNature Communications
Issue number1
Number of pages15
Publication statusPublished - 2023


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