Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae

Andrej Benjak, Charlotte Avanzi, Pushpendra Singh, Chloé Loiseau, Selfu Girma, Philippe Busso, Amanda N. Brum Fontes, Yuji Miyamoto, Masako Namisato, Kidist Bobosha, Claudio G. Salgado, Moisés B. Silva, Raquel C. Bouth, Marco A. C. Frade, Fred Bernardes Filho, Josafá G. Barreto, José A. C. Nery, Samira Bührer-Sékula, Andréanne Lupien, Abdul R. Al-Samie, Yasin Al-Qubati, Abdul S. Alkubati, Gisela Bretzel, Lucio Vera-Cabrera, Fatoumata Sakho, Christian R. Johnson, Mamoudou Kodio, Abdoulaye Fomba, Samba O. Sow, Moussa Gado, Ousmane Konaté, Mariane M. A. Stefani, Gerson O. Penna, Philip N. Suffys, Euzenir Nunes Sarno, Milton O. Moraes, Patricia S. Rosa, Ida M. F. Dias Baptista, John S. Spencer, Abraham Aseffa, Masanori Matsuoka, Masanori Kai and Stewart T. Cole ()
Additional contact information
Andrej Benjak: Ecole Polytechnique Fédérale de Lausanne
Charlotte Avanzi: Ecole Polytechnique Fédérale de Lausanne
Pushpendra Singh: Ecole Polytechnique Fédérale de Lausanne
Chloé Loiseau: Ecole Polytechnique Fédérale de Lausanne
Selfu Girma: Armauer Hansen Research Institute
Philippe Busso: Ecole Polytechnique Fédérale de Lausanne
Amanda N. Brum Fontes: Oswaldo Cruz Institute
Yuji Miyamoto: National Institute of Infectious Diseases
Masako Namisato: AUEN Polyclinic
Kidist Bobosha: Armauer Hansen Research Institute
Claudio G. Salgado: Universidade Federal do Pará
Moisés B. Silva: Universidade Federal do Pará
Raquel C. Bouth: Universidade Federal do Pará
Marco A. C. Frade: University of São Paulo
Fred Bernardes Filho: University of São Paulo
Josafá G. Barreto: Federal University of Pará
José A. C. Nery: Oswaldo Cruz Institute
Samira Bührer-Sékula: Federal University of Goiás
Andréanne Lupien: Ecole Polytechnique Fédérale de Lausanne
Abdul R. Al-Samie: c/o National Leprosy Elimination Programme
Yasin Al-Qubati: c/o National Leprosy Elimination Programme
Abdul S. Alkubati: c/o National Leprosy Elimination Programme
Gisela Bretzel: Ludwig-Maximilians-University
Lucio Vera-Cabrera: Universidad Autónoma de Nuevo León
Fatoumata Sakho: Programme National Lèpre de Guinée
Christian R. Johnson: University of Abomey-Calavi
Mamoudou Kodio: Centre National d’Appui à la Lutte Contre la Maladie
Abdoulaye Fomba: Centre National d’Appui à la Lutte Contre la Maladie
Samba O. Sow: Centre National d’Appui à la Lutte Contre la Maladie
Moussa Gado: Ministry of Public Health
Ousmane Konaté: Ministry of Public Health
Mariane M. A. Stefani: Federal University of Goiás
Gerson O. Penna: University of Brasília
Philip N. Suffys: Oswaldo Cruz Institute
Euzenir Nunes Sarno: Oswaldo Cruz Institute
Milton O. Moraes: Oswaldo Cruz Institute
Patricia S. Rosa: Lauro Souza Lima Institute
Ida M. F. Dias Baptista: Lauro Souza Lima Institute
John S. Spencer: Colorado State University
Abraham Aseffa: Armauer Hansen Research Institute
Masanori Matsuoka: National Institute of Infectious Diseases
Masanori Kai: National Institute of Infectious Diseases
Stewart T. Cole: Ecole Polytechnique Fédérale de Lausanne

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-017-02576-z

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