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.

Details

Title
Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae
Author
Benjak, Andrej 1   VIAFID ORCID Logo  ; Avanzi, Charlotte 1 ; Singh, Pushpendra 2 ; Loiseau, Chloé 3   VIAFID ORCID Logo  ; Selfu Girma 4 ; Busso, Philippe 1 ; Brum Fontes, Amanda N 5 ; Miyamoto, Yuji 6 ; Namisato, Masako 7 ; Bobosha, Kidist 4 ; Salgado, Claudio G 8 ; da Silva, Moisés B 8 ; Bouth, Raquel C 8 ; Frade, Marco A C 9 ; Fred Bernardes Filho 9 ; Barreto, Josafá G 10 ; Nery, José A C 11 ; Bührer-Sékula, Samira 12 ; Lupien, Andréanne 1 ; Al-Samie, Abdul R 13 ; Al-Qubati, Yasin 13 ; Alkubati, Abdul S 13 ; Bretzel, Gisela 14 ; Vera-Cabrera, Lucio 15 ; Sakho, Fatoumata 16 ; Johnson, Christian R 17 ; Kodio, Mamoudou 18 ; Fomba, Abdoulaye 18 ; Sow, Samba O 18 ; Gado, Moussa 19 ; Konaté, Ousmane 19 ; Stefani, Mariane M A 12 ; Penna, Gerson O 20 ; Suffys, Philip N 21 ; Euzenir Nunes Sarno 11 ; Moraes, Milton O 11 ; Rosa, Patricia S 22 ; Ida M F Dias Baptista 22 ; Spencer, John S 23 ; Aseffa, Abraham 4   VIAFID ORCID Logo  ; Matsuoka, Masanori 6 ; Kai, Masanori 6 ; Cole, Stewart T 1 

1  Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland 
2  Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Department of Microbiology and Biotechnology Centre, Maharaja Sayajirao University of Baroda, Vadodara, India 
3  Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Tropical and Public Health Institute, Basel, Switzerland 
4  Armauer Hansen Research Institute, Addis Ababa, Ethiopia 
5  Laboratory of Molecular Biology Applied to Mycobacteria, Oswaldo Cruz Institute, Rio de Janeiro, Brazil 
6  Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan 
7  AUEN Polyclinic, Tokorozawa, Saitama Prefecture, Japan 
8  Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Marituba, Pará, Brazil 
9  Dermatology Division, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil 
10  Spatial Epidemiology Laboratory, Federal University of Pará, Castanhal, Pará, Brazil 
11  Leprosy Laboratory, Oswaldo Cruz Institute, Rio de Janeiro, Brazil 
12  Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, Brazil 
13  Ministry of Health and Population, c/o National Leprosy Elimination Programme, Taiz, Yemen 
14  Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-University, Munich, Germany 
15  Laboratorio Interdisciplinario de Investigación Dermatológica, Servicio de Dermatología, Hospital Universitario, Universidad Autónoma de Nuevo León, Monterrey, Mexico 
16  Programme National Lèpre de Guinée, Conakry, Guinea 
17  Centre Interfacultaire de Formation et de Recherche en Environnement pour le Développement Durable, University of Abomey-Calavi, Jericho, Cotonou, Benin 
18  Centre National d’Appui à la Lutte Contre la Maladie, Bamako, Mali 
19  Programme National de Lutte contre la Lèpre, Ministry of Public Health, Niamey, Niger 
20  Tropical Medicine Centre, University of Brasília, Brasília, Brazil 
21  Laboratory of Molecular Biology Applied to Mycobacteria, Oswaldo Cruz Institute, Rio de Janeiro, Brazil; Department of Biomedical Sciences, Mycobacteriology Unit, Tropical Institute of Medicine, Antwerp, Belgium 
22  Lauro Souza Lima Institute, Bauru, São Paulo, Brazil 
23  Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA 
Pages
1-11
Publication year
2018
Publication date
Jan 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-017-02576-z
ProQuest document ID
1990839435
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.