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Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae.

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.

More information

Type
Journal Article
Author
Benjak A
Avanzi C
Singh P
Loiseau C
Girma S
Busso P
Fontes ABN
Miyamoto Y
Namisato M
Bobosha K
Salgado CG
Silva MB
Bouth RC
Frade MA C
Filho FB
Barreto JG
Nery JA C
Bührer-Sékula S
Lupien A
Al-Samie AR
Al-Qubati Y
Alkubati AS
Bretzel G
Vera-Cabrera L
Sakho F
Johnson CR
Kodio M
Fomba A
Sow SO
Gado M
Konaté O
Stefani MM A
Penna GO
Suffys PN
Sarno EN
Moraes MO
Rosa PS
Baptista IDM F
Spencer JS
Aseffa A
Matsuoka M
Kai M
Cole ST
Year of Publication
2018
Journal
Nature communications
Volume
9
Issue
1
Number of Pages
352
Language
eng
ISSN Number
2041-1723
DOI
10.1038/s41467-017-02576-z
Alternate Journal
Nat Commun
Publication Language
eng