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Open Access Highly Accessed Research article

Mycobacterium leprae genomes from a British medieval leprosy hospital: towards understanding an ancient epidemic

Tom A Mendum1*, Verena J Schuenemann2, Simon Roffey3, G Michael Taylor1, Huihai Wu1, Pushpendra Singh4, Katie Tucker3, Jason Hinds5, Stewart T Cole4, Andrzej M Kierzek1, Kay Nieselt6, Johannes Krause5 and Graham R Stewart1

Author Affiliations

1 Department of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, GU2 7XH Guildford, UK

2 Institute for Archaeological Sciences, University of Tübingen, Rümelinstr 23, 72070 Tübingen, Germany

3 Department of Archaeology, University of Winchester, Winchester, UK

4 Global Health Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

5 Bacterial Microarray Group, Division of Cellular and Molecular Medicine, St. George’s, University of London, Cranmer Terrace, London, UK

6 Center for Bioinformatics, University of Tübingen, 72076 Tübingen, Germany

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BMC Genomics 2014, 15:270  doi:10.1186/1471-2164-15-270

Published: 8 April 2014

Abstract

Background

Leprosy has afflicted humankind throughout history leaving evidence in both early texts and the archaeological record. In Britain, leprosy was widespread throughout the Middle Ages until its gradual and unexplained decline between the 14th and 16th centuries. The nature of this ancient endemic leprosy and its relationship to modern strains is only partly understood. Modern leprosy strains are currently divided into 5 phylogenetic groups, types 0 to 4, each with strong geographical links. Until recently, European strains, both ancient and modern, were thought to be exclusively type 3 strains. However, evidence for type 2 strains, a group normally associated with Central Asia and the Middle East, has recently been found in archaeological samples in Scandinavia and from two skeletons from the medieval leprosy hospital (or leprosarium) of St Mary Magdalen, near Winchester, England.

Results

Here we report the genotypic analysis and whole genome sequencing of two further ancient M. leprae genomes extracted from the remains of two individuals, Sk14 and Sk27, that were excavated from 10th-12th century burials at the leprosarium of St Mary Magdalen. DNA was extracted from the surfaces of bones showing osteological signs of leprosy. Known M. leprae polymorphisms were PCR amplified and Sanger sequenced, while draft genomes were generated by enriching for M. leprae DNA, and Illumina sequencing. SNP-typing and phylogenetic analysis of the draft genomes placed both of these ancient strains in the conserved type 2 group, with very few novel SNPs compared to other ancient or modern strains.

Conclusions

The genomes of the two newly sequenced M. leprae strains group firmly with other type 2F strains. Moreover, the M. leprae strain most closely related to one of the strains, Sk14, in the worldwide phylogeny is a contemporaneous ancient St Magdalen skeleton, vividly illustrating the epidemic and clonal nature of leprosy at this site. The prevalence of these type 2 strains indicates that type 2F strains, in contrast to later European and associated North American type 3 isolates, may have been the co-dominant or even the predominant genotype at this location during the 11th century.

Keywords:
Mycobacterium leprae; SNP; Leprosy; Genome; Ancient DNA; Middle Ages; Bioarchaeology