Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae
Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae
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DOI：
10.1038/s41467-017-02576-z
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发表时间：
2018-01-24
影响因子：
16.6
通讯作者：
Cole, Stewart T.
中科院分区：
文献类型：
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作者：
Benjak, Andrej;Avanzi, Charlotte;Cole, Stewart T.
麻风病是一种慢性人类疾病，由尚未培养的病原体麻风分枝杆菌引起。虽然可以用多药疗法（MDT）治愈，但每年仍有超过20万例新病例报告。在这里，我们得到M。麻风病基因组序列直接从病人的皮肤活检提取的DNA使用定制的协议。来自25个国家的154个基因组的比较和系统发育分析提供了对进化和抗菌素耐药性的深入了解，揭示了谱系和地理分布趋势，其中最古老的菌株与远东有关。除了已知的MDT耐药突变外，我们还检测了与抗生素耐药性相关的其他突变，并追溯了MDT前时代广泛耐药的潜在逐步出现。一些以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，第n个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。
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.