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
Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland.
Department of Microbiology and Biotechnology Centre, Maharaja Sayajirao University of Baroda, Vadodara, 390002, India.
Nat Commun. 2018 Jan 24;9(1):352. doi: 10.1038/s41467-017-02576-z.
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.
麻风病是一种由尚未能人工培养的病原体麻风分枝杆菌引起的慢性人类疾病。尽管采用多药联合疗法（MDT）很容易治愈，但每年仍报告有超过20万新病例。在此，我们使用定制方案从直接从患者皮肤活检样本中提取的DNA获得了麻风分枝杆菌基因组序列。对来自25个国家的154个基因组进行的比较和系统发育分析为进化和抗菌耐药性提供了见解，揭示了谱系和系统地理趋势，其中最原始的菌株与远东地区有关。除了已知的耐多药突变外，我们还检测到与抗生素耐药性相关的其他突变，并追溯了在多药联合疗法前时代广泛耐药性可能的逐步出现过程。一些先前未描述的突变发生在明显受到正选择的基因中，其中两个（ribD、fadD9）仅限于耐药菌株。最后，nth切除修复基因中的无义突变与更大的序列多样性和耐药性相关。
