Population Genomics of Mycobacterium leprae Reveals a New Genotype in Madagascar and the Comoros

• Main Authors: Charlotte Avanzi, Emmanuel Lécorché, Fetra Angelot Rakotomalala, Andrej Benjak, Fahafahantsoa Rapelanoro Rabenja, Lala S. Ramarozatovo, Bertrand Cauchoix, Mala Rakoto-Andrianarivelo, Maria Tió-Coma, Thyago Leal-Calvo, Philippe Busso, Stefanie Boy-Röttger, Aurélie Chauffour, Tahinamandrato Rasamoelina, Aina Andrianarison, Fandresena Sendrasoa, John S. Spencer, Pushpendra Singh, Digambar Ramchandra Dashatwar, Rahul Narang, Jean-Luc Berland, Vincent Jarlier, Claudio G. Salgado, Milton O. Moraes, Annemieke Geluk, Andriamira Randrianantoandro, Emmanuelle Cambau, Stewart T. Cole
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-05-01
• Series: Frontiers in Microbiology
• Subjects: leprosy; Mycobacterium leprae; Madagascar; Comoros; genomics; phylogeography
• Online Access: https://www.frontiersin.org/article/10.3389/fmicb.2020.00711/full

Human settlement of Madagascar traces back to the beginning of the first millennium with the arrival of Austronesians from Southeast Asia, followed by migrations from Africa and the Middle East. Remains of these different cultural, genetic, and linguistic legacies are still present in Madagascar and other islands of the Indian Ocean. The close relationship between human migration and the introduction and spread of infectious diseases, a well-documented phenomenon, is particularly evident for the causative agent of leprosy, Mycobacterium leprae. In this study, we used whole-genome sequencing (WGS) and molecular dating to characterize the genetic background and retrace the origin of the M. leprae strains circulating in Madagascar (n = 30) and the Comoros (n = 3), two islands where leprosy is still considered a public health problem and monitored as part of a drug resistance surveillance program. Most M. leprae strains (97%) from Madagascar and Comoros belonged to a new genotype as part of branch 1, closely related to single nucleotide polymorphism (SNP) type 1D, named 1D-Malagasy. Other strains belonged to the genotype 1A (3%). We sequenced 39 strains from nine other countries, which, together with previously published genomes, amounted to 242 genomes that were used for molecular dating. Specific SNP markers for the new 1D-Malagasy genotype were used to screen samples from 11 countries and revealed this genotype to be restricted to Madagascar, with the sole exception being a strain from Malawi. The overall analysis thus ruled out a possible introduction of leprosy by the Austronesian settlers and suggests a later origin from East Africa, the Middle East, or South Asia.