Phylogenomics and antimicrobial resistance of the leprosy bacillus mycobacterium leprae

École Polytechnique Fédérale de Lausanne. Global Health Institute. Lausanne, Switzerland.
École Polytechnique Fédérale de Lausanne. Global Health Institute. Lausanne, Switzerland.
École Polytechnique Fédérale de Lausanne. Global Health Institute. Lausanne, Switzerland / Maharaja Sayajirao University of Baroda. Department of Microbiology and Biotechnology Centre. Vadodara, Gujarat, India.
École Polytechnique Fédérale de Lausanne. Global Health Institute. Lausanne, Switzerland / Swiss Tropical and Public Health Institute. Basel, Switzerland.
Armauer Hansen Research Institute. Addis Ababa, Ethiopia.
École Polytechnique Fédérale de Lausanne. Global Health Institute. Lausanne, Switzerland.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.
National Institute of Infectious Diseases. Leprosy Research Center. Higashimurayama, Tokyo, Japan.
AUEN Polyclinic. Department of Dermatology. Nakatomi, Tokorozawa, Saitama-prefecture, Japan.
Armauer Hansen Research Institute. Addis Ababa, Ethiopia.
Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Dermato-Imunologia. Belém, PA, Brasil.
Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Dermato-Imunologia. Belém, PA, Brasil.
Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Dermato-Imunologia. Belém, PA, Brasil.
Universidade de São Paulo. Faculdade de Medicina. Departamento de Clínica Médica. Dermatologia. Ribeirão Preto, SP, Brasil.
Universidade de São Paulo. Faculdade de Medicina. Departamento de Clínica Médica. Dermatologia. Ribeirão Preto, SP, Brasil.
Universidade Federal do Pará. Laboratório de Epidemiologia Espacial. Castanhal, PA, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Universidade Federal de Goiás. Instituto de Patologia Tropical e Saúde Pública. Goiânia, GO, Brasil.
École Polytechnique Fédérale de Lausanne. Global Health Institute. Lausanne, Switzerland.
Ministry of Public Health and Population. Sana'a, Yemen / National Leprosy Elimination Programme. Taiz, Yemen.
Ministry of Public Health and Population. Sana'a, Yemen / National Leprosy Elimination Programme. Taiz, Yemen.
Ministry of Public Health and Population. Sana'a, Yemen / National Leprosy Elimination Programme. Taiz, Yemen.
Ludwig-Maximilians-University. University Hospital. Division of Infectious Diseases and Tropical Medicine. Munich, Germany.
Universidad Autónoma de Nuevo León. Hospital Universitario. Servicio de Dermatología. Laboratorio Interdisciplinario de Investigación Dermatológica. Monterrey, Mexico.
Programme National Lèpre de Guinée. Conakry, Guinea.
University of Abomey-Calavi. Centre Interfacultaire de Formation et de Recherche en Environnement pour le Développement Durable. Jericho, Cotonou, Benin.
Centre National d’Appui à la Lutte Contre la Maladie. Bamako, Mali.
Centre National d’Appui à la Lutte Contre la Maladie. Bamako, Mali.
Centre National d’Appui à la Lutte Contre la Maladie. Bamako, Mali.
Ministry of Public Health. Programme National de Lutte contre la Lèpre. Niamey, Niger.
Ministry of Public Health. Programme National de Lutte contre la Lèpre. Niamey, Niger.
Universidade Federal de Goiás. Instituto de Patologia Tropical e Saúde Pública. Goiânia, GO, Brasil.
Universidade de Brasília. Núcleo de Medicina Tropical. Brasília, DF, Brasil / Fundação Oswaldo Cruz. Fiocruz Brasília. Brasília, DF, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil / Tropical Institute of Medicine. Mycobacteriology Unit. Department of Biomedical Sciences. Antwerp, Belgium.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Instituto Lauro de Souza Lima. Bauru, SP, Brasil.
Instituto Lauro de Souza Lima. Bauru, SP, Brasil.
Colorado State University. Department of Microbiology, Immunology, and Pathology. Fort Collins, CO, USA.
Armauer Hansen Research Institute. Addis Ababa, Ethiopia.
National Institute of Infectious Diseases. Leprosy Research Center. Higashimurayama, Tokyo, Japan.
National Institute of Infectious Diseases. Leprosy Research Center. Higashimurayama, Tokyo, Japan.
École Polytechnique Fédérale de Lausanne. Global Health Institute. Lausanne, Switzerland.

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.

Keywords in Portuguese

Genoma bacteriano
Microbiologia clínica
Patógenos
Mycobacterium leprae
Filogenômica
Resistência antimicrobiana
Hanseníase

Keywords

Bacterial genomics
Clinical microbiology
Pathogens
Mycobacterium leprae
Phylogenomics
Antimicrobial resistance
Leprosy

Publisher

Nature Publishing Group

Citation

BENJAK, Andrej et al. Phylogenomics and antimicrobial resistance of the leprosy bacillus mycobacterium leprae. Nature Communications, v. 9, n. 352, p. 1-11, 24 Jan. 2018.

DOI

10.1038/s41467-017-02576-z

ISSN

2041-1723

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/26630

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Open access

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