4,000-year-old Mycobacterium lepromatosis genomes from Chile reveal long establishment of Hansen’s disease in the Americas

Mycobacterium lepromatosis is a recently identified cause of Hansen’s disease, and is associated with the more severe and potentially lethal presentations of diffuse lepromatous leprosy and Lucio’s phenomenon. Detection of this infection has been limited to a small number of individuals, leaving much to be learned about its global distribution and transmissibility. Its discovery in wild rodent populations in the United Kingdom and Ireland also raises questions about its zoonotic potential. Here, we raise further awareness of this disease via analyses of two exceptionally well preserved M. lepromatosis genomes obtained from 4,000-year-old human remains of two adult males from the archaeological sites of El Cerrito and La Herradura in Northern Chile. This formed the basis of genomic comparisons between ancient and modern forms of the pathogen. We demonstrate an unexpected long history of M. lepromatosis in the Americas, which contrasts with the more recent Eurasian history of the closely related Mycobacterium leprae. We offer relevant perspectives on its evolution while providing an incentive for further disease monitoring in both humans and other potential reservoir species in the Americas and elsewhere.