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Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae. 2018
Andrej Benjak, and
Charlotte Avanzi, and
Pushpendra Singh, and
Chloé Loiseau, and
Selfu Girma, and
Philippe Busso, and
Amanda N Brum Fontes, and
Yuji Miyamoto, and
Masako Namisato, and
Kidist Bobosha, and
Claudio G Salgado, and
Moisés B da Silva, and
Raquel C Bouth, and
Marco A C Frade, and
Fred Bernardes Filho, and
Josafá G Barreto, and
José A C Nery, and
Samira Bührer-Sékula, and
Andréanne Lupien, and
Abdul R Al-Samie, and
Yasin Al-Qubati, and
Abdul S Alkubati, and
Gisela Bretzel, and
Lucio Vera-Cabrera, and
Fatoumata Sakho, and
Christian R Johnson, and
Mamoudou Kodio, and
Abdoulaye Fomba, and
Samba O Sow, and
Moussa Gado, and
Ousmane Konaté, and
Mariane M A Stefani, and
Gerson O Penna, and
Philip N Suffys, and
Euzenir Nunes Sarno, and
Milton O Moraes, and
Patricia S Rosa, and
Ida M F Dias Baptista, and
John S Spencer, and
Abraham Aseffa, and
Masanori Matsuoka, and
Masanori Kai, and
Stewart T Cole
Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland.
Leprosy is a chronic human disease caused by the yet-uncultured pathogen Mycobacterium leprae. Although readily curable with multidrug therapy (MDT), over 200,000 new cases are still reported annually. Here, we obtain M. leprae genome sequences from DNA extracted directly from patients' skin biopsies using a customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25 countries provides insight into evolution and antimicrobial resistance, uncovering lineages and phylogeographic trends, with the most ancestral strains linked to the Far East. In addition to known MDT-resistance mutations, we detect other mutations associated with antibiotic resistance, and retrace a potential stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the previously undescribed mutations occur in genes that are apparently subject to positive selection, and two of these (ribD, fadD9) are restricted to drug-resistant strains. Finally, nonsense mutations in the nth excision repair gene are associated with greater sequence diversity and drug resistance.
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