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author Benjak, Andrej
Avanzi, Charlotte
Singh, Pushpendra
Loiseau, Chloé
Girma, Selfu
Busso, Philippe
Fontes, Amanda N. Brum
Miyamoto, Yuji
Namisato, Masako
Bobosha, Kidist
Salgado, Claudio G.
Da Silva, Moisés B.
Bouth, Raquel C.
Frade, Marco A. C.
Filho, Fred Bernardes
Barreto, Josafá G.
Nery, José A. C.
Bührer Sékula, Samira
Lupien, Andréanne
Al Samie, Abdul R.
Al Qubati, Yasin
Alkubati, Abdul S.
Bretzel, Gisela
Vera Cabrera, Lucio
Sakho, Fatoumata
Johnson, Christian R.
Kodio, Mamoudou
Fomba, Abdoulaye
Sow, Samba O.
Gado, Moussa
Konaté, Ousmane
Stefani, Mariane M. A.
Penna, Gerson O.
Suffys, Philip N.
Sarno, Euzenir Nunes
Moraes, Milton O.
Rosa, Patricia S.
Baptista, Ida M. F. Dias
Spencer, John S.
Aseffa, Abraham
Matsuoka, Masanori
Kai, Masanori
Cole, Stewart T.
author_facet Benjak, Andrej
Avanzi, Charlotte
Singh, Pushpendra
Loiseau, Chloé
Girma, Selfu
Busso, Philippe
Fontes, Amanda N. Brum
Miyamoto, Yuji
Namisato, Masako
Bobosha, Kidist
Salgado, Claudio G.
Da Silva, Moisés B.
Bouth, Raquel C.
Frade, Marco A. C.
Filho, Fred Bernardes
Barreto, Josafá G.
Nery, José A. C.
Bührer Sékula, Samira
Lupien, Andréanne
Al Samie, Abdul R.
Al Qubati, Yasin
Alkubati, Abdul S.
Bretzel, Gisela
Vera Cabrera, Lucio
Sakho, Fatoumata
Johnson, Christian R.
Kodio, Mamoudou
Fomba, Abdoulaye
Sow, Samba O.
Gado, Moussa
Konaté, Ousmane
Stefani, Mariane M. A.
Penna, Gerson O.
Suffys, Philip N.
Sarno, Euzenir Nunes
Moraes, Milton O.
Rosa, Patricia S.
Baptista, Ida M. F. Dias
Spencer, John S.
Aseffa, Abraham
Matsuoka, Masanori
Kai, Masanori
Cole, Stewart T.
author_sort Benjak, Andrej
collection Repositorio Institucional
description 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.
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spelling eprints-159712024-12-10T15:29:28Z http://eprints.uanl.mx/15971/ Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae Benjak, Andrej Avanzi, Charlotte Singh, Pushpendra Loiseau, Chloé Girma, Selfu Busso, Philippe Fontes, Amanda N. Brum Miyamoto, Yuji Namisato, Masako Bobosha, Kidist Salgado, Claudio G. Da Silva, Moisés B. Bouth, Raquel C. Frade, Marco A. C. Filho, Fred Bernardes Barreto, Josafá G. Nery, José A. C. Bührer Sékula, Samira Lupien, Andréanne Al Samie, Abdul R. Al Qubati, Yasin Alkubati, Abdul S. Bretzel, Gisela Vera Cabrera, Lucio Sakho, Fatoumata Johnson, Christian R. Kodio, Mamoudou Fomba, Abdoulaye Sow, Samba O. Gado, Moussa Konaté, Ousmane Stefani, Mariane M. A. Penna, Gerson O. Suffys, Philip N. Sarno, Euzenir Nunes Moraes, Milton O. Rosa, Patricia S. Baptista, Ida M. F. Dias Spencer, John S. Aseffa, Abraham Matsuoka, Masanori Kai, Masanori Cole, Stewart T. RL Dermatología 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. 2018 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/15971/1/44.pdf http://eprints.uanl.mx/15971/1.haspreviewThumbnailVersion/44.pdf Benjak, Andrej y Avanzi, Charlotte y Singh, Pushpendra y Loiseau, Chloé y Girma, Selfu y Busso, Philippe y Fontes, Amanda N. Brum y Miyamoto, Yuji y Namisato, Masako y Bobosha, Kidist y Salgado, Claudio G. y Da Silva, Moisés B. y Bouth, Raquel C. y Frade, Marco A. C. y Filho, Fred Bernardes y Barreto, Josafá G. y Nery, José A. C. y Bührer Sékula, Samira y Lupien, Andréanne y Al Samie, Abdul R. y Al Qubati, Yasin y Alkubati, Abdul S. y Bretzel, Gisela y Vera Cabrera, Lucio y Sakho, Fatoumata y Johnson, Christian R. y Kodio, Mamoudou y Fomba, Abdoulaye y Sow, Samba O. y Gado, Moussa y Konaté, Ousmane y Stefani, Mariane M. A. y Penna, Gerson O. y Suffys, Philip N. y Sarno, Euzenir Nunes y Moraes, Milton O. y Rosa, Patricia S. y Baptista, Ida M. F. Dias y Spencer, John S. y Aseffa, Abraham y Matsuoka, Masanori y Kai, Masanori y Cole, Stewart T. (2018) Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae. Nature Communications, 9 (1). pp. 1-11. ISSN 2041-1723 http://doi.org/10.1038/s41467-017-02576-z doi:10.1038/s41467-017-02576-z
spellingShingle RL Dermatología
Benjak, Andrej
Avanzi, Charlotte
Singh, Pushpendra
Loiseau, Chloé
Girma, Selfu
Busso, Philippe
Fontes, Amanda N. Brum
Miyamoto, Yuji
Namisato, Masako
Bobosha, Kidist
Salgado, Claudio G.
Da Silva, Moisés B.
Bouth, Raquel C.
Frade, Marco A. C.
Filho, Fred Bernardes
Barreto, Josafá G.
Nery, José A. C.
Bührer Sékula, Samira
Lupien, Andréanne
Al Samie, Abdul R.
Al Qubati, Yasin
Alkubati, Abdul S.
Bretzel, Gisela
Vera Cabrera, Lucio
Sakho, Fatoumata
Johnson, Christian R.
Kodio, Mamoudou
Fomba, Abdoulaye
Sow, Samba O.
Gado, Moussa
Konaté, Ousmane
Stefani, Mariane M. A.
Penna, Gerson O.
Suffys, Philip N.
Sarno, Euzenir Nunes
Moraes, Milton O.
Rosa, Patricia S.
Baptista, Ida M. F. Dias
Spencer, John S.
Aseffa, Abraham
Matsuoka, Masanori
Kai, Masanori
Cole, Stewart T.
Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae
thumbnail https://rediab.uanl.mx/themes/sandal5/images/online.png
title Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae
title_full Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae
title_fullStr Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae
title_full_unstemmed Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae
title_short Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae
title_sort phylogenomics and antimicrobial resistance of the leprosy bacillus mycobacterium leprae
topic RL Dermatología
url http://eprints.uanl.mx/15971/1/44.pdf
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