02508nas a2200313 4500000000100000008004100001260001600042653002100058653001800079653002400097653004000121100001200161700001200173700001300185700002000198700001400218700002200232700001200254700001300266700002000279700001300299700001400312700001900326245010200345856007000447300000900517520165400526022001402180 2024 d bElsevier BV10amedieval England10ared squirrels10aanimal leprosy host10aAncient Mycobacterium leprae genome1 aUrban C1 aBlom AA1 aAvanzi C1 aWalker-Meikle K1 aWarren AK1 aWhite-Iribhogbe K1 aTurle R1 aMarter P1 aDawson-Hobbis H1 aRoffey S1 aInskip SA1 aSchuenemann VJ00aAncient Mycobacterium leprae genome reveals medieval English red squirrels as animal leprosy host uhttps://www.cell.com/action/showPdf?pii=S0960-9822%2824%2900446-9 a1-103 a

Leprosy, one of the oldest recorded diseases in human history, remains prevalent in Asia, Africa, and South America, with over 200,000 cases every year. Although ancient DNA (aDNA) approaches on the major causative agent, Mycobacterium leprae, have elucidated the disease’s evolutionary history, the role of animal hosts and interspecies transmission in the past remains unexplored. Research has uncovered relationships between medieval strains isolated from archaeological human remains and modern animal hosts such as the red squirrel in England. However, the time frame, distribution, and direction of transmissions remains unknown. Here, we studied 25 human and 12 squirrel samples from two archaeological sites in Winchester, a medieval English city well known for its leprosarium and connections to the fur trade. We reconstructed four medieval M. leprae genomes, including one from a red squirrel, at a 2.2-fold average coverage. Our analysis revealed a phylogenetic placement of all strains on branch 3 as well as a close relationship between the squirrel strain and one newly reconstructed medieval human strain. In particular, the medieval squirrel strain is more closely related to some medieval human strains from Winchester than to modern red squirrel strains from England, indicating a yet-undetected circulation of M. leprae in non-human hosts in the Middle Ages. Our study represents the first One Health approach for M. leprae in archaeology, which is centered around a medieval animal host strain, and highlights the future capability of such approaches to understand the disease’s zoonotic past and current potential.

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