02706nas a2200685   4500000000100000008004100001653002900042653001200071653002800083653001800111100001300129700001300142700001200155700001400167700001200181700001200193700001400205700001500219700001500234700001400249700001500263700001300278700001200291700001300303700001300316700001400329700001200343700002200355700001300377700001500390700001600405700001500421700001400436700001900450700001200469700001400481700001200495700001200507700001000519700001100529700001400540700001400554700001200568700001300580700001200593700001300605700001200618700001900630700001500649700001300664700001500677700001000692700001100702245009300713856008900806300000800895490000600903520109700909022001402006       2018                            d10aAntimicrobial resistance10aleprosy10aMultidrug therapy (MDT)10aPhylogenomics1 aBenjak A1 aAvanzi C1 aSingh P1 aLoiseau C1 aGirma S1 aBusso P1 aFontes AB1 aMiyamoto Y1 aNamisato M1 aBobosha K1 aSalgado CG1 aSilva MB1 aBouth R1 aFrade MA1 aFilho FB1 aBarreto J1 aNery JA1 aBührer-Sékula S1 aLupien A1 aAl-Samie A1 aAl-Qubati Y1 aAlkubati A1 aBretzel G1 aVera-Cabrera L1 aSakho F1 aJohnson C1 aKodio M1 aFomba A1 aSow S1 aGado M1 aKonaté O1 aStefani M1 aPenna G1 aSuffys P1 aSarno E1 aMoraes M1 aRosa PS1 aBaptista IDM F1 aSpencer JS1 aAseffa A1 aMatsuoka M1 aKai M1 aCole S00aPhylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783932/pdf/41467_2017_Article_2576.pdf  a3520 v93 a<p>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.</p>
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