@article{31099,
  keywords = {Antimicrobial resistance, leprosy, Multidrug therapy (MDT), Phylogenomics},
  author = {Benjak A and Avanzi C and Singh P and Loiseau C and Girma S and Busso P and Fontes AB and Miyamoto Y and Namisato M and Bobosha K and Salgado CG and Silva MB and Bouth R and Frade MA and Filho FB and Barreto J and Nery JA and Bührer-Sékula S and Lupien A and Al-Samie A and Al-Qubati Y and Alkubati A and Bretzel G and Vera-Cabrera L and Sakho F and Johnson C and Kodio M and Fomba A and Sow S and Gado M and Konaté O and Stefani M and Penna G and Suffys P and Sarno E and Moraes M and Rosa PS and Baptista IDM F and Spencer JS and Aseffa A and Matsuoka M and Kai M and Cole S},
  title = {Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae.},
  abstract = {<p>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.</p>
},
  year = {2018},
  journal = {Nature communications},
  volume = {9},
  pages = {352},
  issn = {2041-1723},
  url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783932/pdf/41467_2017_Article_2576.pdf},
  doi = {10.1038/s41467-017-02576-z},
  language = {eng},
}