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.

Detection ofMycobacterium lepraeDNA in soil; Multiple needles in the haystack?

“…In previous phylogeographic analysis SNP type 1 was identified as the predominant strain type in South Asia(29, 30) and was likely introduced to South Asia from other parts of that continent(30). The SNP type found in soil samples from Bangladesh (SNP type 1) is therefore in accordance with previous phylogeographic data(29).…”

Islam, Leprosy, and Disability: How Religion, History, Art, and Storytelling Can Yield New Insights and Acceptance

“…Although the exact origin of leprosy is poorly understood, a combination of three methodologies has provided insights into its origins and spread throughout the world: comparative genomics (which compares DNA sequences among different organisms for clues to their geographic origins and evolution), classical paleopathogy (which studies ancient diseases based on evidence from fossils, skeletons, and other remains), and ancient writings. Regarding the first approach, recent comparative genomic studies suggest that the main causative bacterium, Mycobacterium leprae, evolved in either East Africa or South Asia during the Late Pleistocene (which ended about 11,700 years ago) [14,15]. From there, leprosy spread through successive migrations to Europe and the rest of the world [14].…”

“…Potentially supporting this view, a recent genetic analysis of M. leprae estimated that the most common recent ancestor of the microorganism dates to 2543 BC to AD 36. As for paleopathological evidence, the oldest documented skeletal evidence suggests that the lepromatous form of leprosy was present in India by 2000 BC [14,15]. Finally, the earliest widely accepted written record of leprosy is from Asian texts dating to 600 BC [14,15].…”

“…As for paleopathological evidence, the oldest documented skeletal evidence suggests that the lepromatous form of leprosy was present in India by 2000 BC [14,15]. Finally, the earliest widely accepted written record of leprosy is from Asian texts dating to 600 BC [14,15]. Despite the intriguing clues gathered from all three methodologies, it should be kept in mind that the origin of leprosy is an active area of research and that the final word has not yet been written.…”

“…13 In a third hadith (graded as sound), it is said that Prophet Muhammad asked an individual with leprosy to join him for a meal and actually took the man's hand and put it in a dish 14 [12], telling him, "Eat, in the name of Allah, trusting in Allah and putting your reliance in Him." 15 Over the centuries, the three hadiths 16 reproduced above have been extensively discussed and debated by Muslim scholars 17 . To resolve the apparent contradictions among them, it is important to 11 The narration can be found in the hadith compilation of Ahmad, and also in the canonical compilation of Bukhari; see 'Asqalani [17] (vol.…”