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Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae

Author

Listed:
  • Andrej Benjak

    (Ecole Polytechnique Fédérale de Lausanne)

  • Charlotte Avanzi

    (Ecole Polytechnique Fédérale de Lausanne)

  • Pushpendra Singh

    (Ecole Polytechnique Fédérale de Lausanne
    Maharaja Sayajirao University of Baroda)

  • Chloé Loiseau

    (Ecole Polytechnique Fédérale de Lausanne
    Swiss Tropical and Public Health Institute)

  • 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
    Tropical Institute of Medicine)

  • 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)

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.

Suggested Citation

  • 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 & Moi, 2018. "Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02576-z
    DOI: 10.1038/s41467-017-02576-z
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