Phylogenomics and Zoonotic Spillover of <i>Mycobacterium leprae</i> in the Pacific Islands and Brazil

Leprosy, or Hansen’s disease, is often relegated to antiquity, yet it remains a modern public health concern with around 200,000 new cases reported annually around the world (World Health Organization, 2023). Most leprosy cases in humans are caused by Mycobacterium leprae, but a small number of cases are now known to be caused by Mycobacterium lepromatosis, which is found mostly in Mexico and the Caribbean (Han et al., 2008; 2012). Recent work has improved our understanding of the pattern of genomic variation in M. leprae strains, however certain regions remain understudied. Additionally, ongoing surveillance has identified pockets of hyperendemicity, which could act as hotspots for the spread of drug-resistant strains. Despite increased surveillance, there has been limited genomic research in regions like the Pacific and few surveys incorporating a broad species range in endemic areas. To address this, M. leprae genomes were isolated from clinical formalin-fixed, paraffin-embedded (FFPE) samples from the Pacific Islands and used in phylogenetic and phylogeographic analyses. 21 novel M. leprae strains from these samples were sequenced and dating analyses determined that M. leprae strains have been circulating in the Pacific since the original peopling of the region. Furthermore, recent radiation events among the Pacific Islands, as well as a rise in drug-resistant M. leprae strains, were identified and described. Additionally, a survey of animals in an endemic state in Brazil resulted in the first M. leprae genome isolated from a big cat. This body of research leverages genomic data to characterize novel diversity of M. leprae strains, identify drug-resistant strains in these regions, and determine how this pathogen spreads through space and time. The results of this work will aid in our understanding of the history of leprosy and improve public health responses to this disease.