Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae
Benjak, A.; Avanzi, C.; Singh, P.; Loiseau, C.; Girma, S.; Busso, P.; Fontes, A. N. B.; Miyamoto, Y.; Namisato, M.; Bobosha, K.; Salgado, C. G.; da Silva, M. B.; Bouth, R. C.; Frade, M. A. C.; Filho, F. B.; Barreto, J. G.; Nery, J. A. C.; Buhrer-Sekula, S.; Lupien, A.; Al-Samie, A. R.; Al-Qubati, Y.; Alkubati, A. S.; Bretzel, G.; Vera-Cabrera, L.; Sakho, F.; Johnson, C. R.; Kodio, M.; Fomba, A.; Sow, S. O.; Gado, M.; Konate, O.; Stefani, M. M. A.; Penna, G. O.; Suffys, P. N.; Sarno, E. N.; Moraes, M.O.; Rosa, P. S.; Baptista, I. M. F. D.; Spencer, J. S.; Aseffa, A.; Matsuoka, M.; Kai, M.; Cole, S. T.
Journal Name:
Nature Communications
Keywords:
Mycobacterium leprae
Bacteriology
Phylogenomics
Leprosy
Bacterial diseases
Drug resistance
Global
Global health
Health
Switzerland
Microbiology
Biotechnology
Universities
India
Tropical
Public
Public health
Research
Addis Ababa
Ethiopia
Laboratory
Laboratories
Molecular
Molecular biology
Biology
Mycobacteria
Mycobacterium
Brazil
National
Infectious diseases
Diseases
Disease
Japan
Dermatology
Medical
School
Epidemiology
Pathology
Population
Elimination
Yemen
Tropical medicine
Medicine
Hospital
Germany
Mexico
Guinea
Cotonou
Benin
Mali
Niger
Science
Mycobacteriology
Antwerp
Belgium
Immunology
USA
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.
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