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Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae

Benjak, Andrej and Avanzi, Charlotte and Singh, Pushpendra and Loiseau, Chloé and Girma, Selfu and Busso, Philippe and Fontes, Amanda N. Brum and Miyamoto, Yuji and Namisato, Masako and Bobosha, Kidist and Salgado, Claudio G. and da Silva, Moisés B. and Bouth, Raquel C. and Frade, Marco A. C. and Filho, Fred Bernardes and Barreto, Josafá G. and Nery, José A. C. and Bührer-Sékula, Samira and Lupien, Andréanne and Al-Samie, Abdul R. and Al-Qubati, Yasin and Alkubati, Abdul S. and Bretzel, Gisela and Vera-Cabrera, Lucio and Sakho, Fatoumata and Johnson, Christian R. and Kodio, Mamoudou and Fomba, Abdoulaye and Sow, Samba O. and Gado, Moussa and Konaté, Ousmane and Stefani, Mariane M. A. and Penna, Gerson O. and Suffys, Philip N. and Sarno, Euzenir Nunes and Moraes, Milton O. and Rosa, Patricia S. and Baptista, Ida M. F. Dias and Spencer, John S. and Aseffa, Abraham and Matsuoka, Masanori and Kai, Masanori and Cole, Stewart T.. (2018) Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae. Nature Communications, 9. p. 352.

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Ecology and Evolution Unit (Gagneux)
UniBasel Contributors:Loiseau, Chloé Marie and Loiseau, Chloé Marie
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
e-ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:14 Sep 2018 12:42
Deposited On:25 Jun 2018 13:14

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