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 () and Andrew C. Doxey ()
Additional contact information
Harold P. Hodgins: University of Waterloo
Pengsheng Chen: Boston Children’s Hospital
Briallen Lobb: University of Waterloo
Xin Wei: University of Waterloo
Benjamin J. M. Tremblay: University of Waterloo
Michael J. Mansfield: Okinawa Institute of Science and Technology Graduate University
Victoria C. Y. Lee: University of Waterloo
Pyung-Gang Lee: Boston Children’s Hospital
Jeffrey Coffin: University of Waterloo
Ana T. Duggan: McMaster University
Alexis E. Dolphin: University of Waterloo
Gabriel Renaud: Technical University of Denmark
Min Dong: Boston Children’s Hospital
Andrew C. Doxey: University of Waterloo

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-41174-0

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