Multi-omic detection of Mycobacterium leprae in archaeological human dental calculus

Author:

Fotakis Anna K.1ORCID,Denham Sean D.2ORCID,Mackie Meaghan13ORCID,Orbegozo Miren Iraeta1ORCID,Mylopotamitaki Dorothea1ORCID,Gopalakrishnan Shyam1ORCID,Sicheritz-Pontén Thomas1ORCID,Olsen Jesper V.3ORCID,Cappellini Enrico1ORCID,Zhang Guojie4567ORCID,Christophersen Axel8ORCID,Gilbert M. Thomas P.18ORCID,Vågene Åshild J.1ORCID

Affiliation:

1. Section for Evolutionary Genomics, GLOBE Institute, Faculty of Health and Medical Sciences, University of Stavanger, Stavanger, Norway

2. Museum of Archaeology, University of Stavanger, Stavanger, Norway

3. Novo Nordisk Foundation Centre for Protein Research, University of Copenhagen, Copenhagen, Denmark

4. Section for Ecology and Evolution, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark

5. BGI-Shenzhen, 518083 Shenzhen, People's Republic of China

6. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 650223 Kunming, People's Republic of China

7. Centre for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, 650223 Kunming, People's Republic of China

8. NTNU University Museum, Trondheim, Norway

Abstract

Mineralized dental plaque (calculus) has proven to be an excellent source of ancient biomolecules. Here we present a Mycobacterium leprae genome (6.6-fold), the causative agent of leprosy, recovered via shotgun sequencing of sixteenth-century human dental calculus from an individual from Trondheim, Norway. When phylogenetically placed, this genome falls in branch 3I among the diversity of other contemporary ancient strains from Northern Europe. Moreover, ancient mycobacterial peptides were retrieved via mass spectrometry-based proteomics, further validating the presence of the pathogen. Mycobacterium leprae can readily be detected in the oral cavity and associated mucosal membranes, which likely contributed to it being incorporated into this individual's dental calculus. This individual showed some possible, but not definitive, evidence of skeletal lesions associated with early-stage leprosy. This study is the first known example of successful multi-omics retrieval of M. leprae from archaeological dental calculus. Furthermore, we offer new insights into dental calculus as an alternative sample source to bones or teeth for detecting and molecularly characterizing M. leprae in individuals from the archaeological record. This article is part of the theme issue ‘Insights into health and disease from ancient biomolecules’.

Funder

Carlsbergfondet

Villum Fonden

Novo Nordisk Fonden

Lundbeckfonden

Norges Forskningsråd

Publisher

The Royal Society

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology

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