Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae

被引：83

作者：

Benjak, Andrej ^{[1
]}

Avanzi, Charlotte ^{[1
]}

Singh, Pushpendra ^{[1
,2
,3
]}

Loiseau, Chloe ^{[1
,4
]}

Girma, Selfu ^{[5
]}

Busso, Philippe ^{[1
]}

Brum Fontes, Amanda N. ^{[6
]}

Miyamoto, Yuji ^{[7
]}

Namisato, Masako ^{[8
]}

Bobosha, Kidist ^{[5
]}

Salgado, Claudio G. ^{[9
]}

da Silva, Moises B. ^{[9
]}

Bouth, Raquel C. ^{[9
]}

Frade, Marco A. C. ^{[10
]}

Bernardes Filho, Fred ^{[10
]}

Barreto, Josafa G. ^{[11
]}

Nery, Jose A. C. ^{[12
]}

Buehrer-Sekula, Samira ^{[13
]}

Lupien, Andreanne ^{[1
]}

Al-Samie, Abdul R. ^{[14
]}

Al-Qubati, Yasin

Alkubati, Abdul S. ^{[14
]}

Bretzel, Gisela ^{[15
]}

Vera-Cabrera, Lucio ^{[16
]}

Sakho, Fatoumata ^{[17
]}

Johnson, Christian R. ^{[18
]}

Kodio, Mamoudou ^{[19
]}

Fomba, Abdoulaye ^{[19
]}

Sow, Samba O. ^{[19
]}

Gado, Moussa ^{[20
]}

Konate, Ousmane ^{[20
]}

Stefani, Mariane M. A. ^{[13
]}

Penna, Gerson O. ^{[21
]}

Suffys, Philip N. ^{[6
,22
]}

Sarno, Euzenir Nunes ^{[12
]}

Moraes, Milton O. ^{[12
]}

Rosa, Patricia S. ^{[23
]}

Dias Baptista, Ida M. F. ^{[23
]}

Spencer, John S. ^{[24
]}

Aseffa, Abraham ^{[5
]}

Matsuoka, Masanori ^{[7
]}

Kai, Masanori ^{[7
]}

Cole, Stewart T. ^{[1
]}

机构：

[1] Ecole Polytech Fed Lausanne, Global Hlth Inst, CH-1015 Lausanne, Switzerland

[2] Maharaja Sayajirao Univ Baroda, Dept Microbiol, Vadodara 390002, India

[3] Maharaja Sayajirao Univ Baroda, Biotechnol Ctr, Vadodara 390002, India

[4] Swiss Trop & Publ Hlth Inst, CH-4051 Basel, Switzerland

[5] Armauer Hansen Res Inst, POB 1005, Addis Ababa, Ethiopia

[6] Fiocruz MS, Oswaldo Cruz Inst, Lab Mol Biol Appl Mycobacteria, BR-21040360 Rio De Janeiro, Brazil

[7] Natl Inst Infect Dis, Leprosy Res Ctr, Higashimurayama, Tokyo 1890002, Japan

[8] AUEN Polyclin, Tokorozawa, Saitama 3590002, Japan

[9] Univ Fed Para, Inst Ciencias Biol, Lab Dermato Imunol, BR-67200000 Marituba, Para, Brazil

[10] Univ Sao Paulo, Ribeirao Preto Med Sch, Dermatol Div, BR-14049900 Ribeirao Preto, SP, Brazil

[11] Fed Univ Para, Spatial Epidemiol Lab, BR-68746360 Castanhal, Para, Brazil

[12] Fiocruz MS, Oswaldo Cruz Inst, Leprosy Lab, BR-21040900 Rio De Janeiro, Brazil

[13] Univ Fed Goias, Trop Pathol & Publ Hlth Inst, BR-74605050 Goiania, Go, Brazil

[14] Ministry Hlth & Populat, Natl Leprosy Eliminat Programme, Taizi, Yemen

[15] Ludwig Maximilians Univ Munchen, Div Infect Dis & Trop Med, Univ Hosp, D-80802 Munich, Germany

[16] Univ Autonoma Nuevo, Hosp Univ, Lab Interdisciplinario Invest Dermatol, Serv Dermatol, Monterrey 64460, Mexico

[17] Programme Natl Lepre Guinee, Conakry, Guinea

[18] Univ Abomey Calavi, Ctr Interfac Format & Rech Environm Dev, 03 BP 1463 Jericho, Cotonou, Benin

[19] Ctr Natl Appui Lutte Maladie, Bamako, Mali

[20] Minist Publ Hlth, Programme Natl Lutte Lepre, Niamey, Niger

[21] Univ Brasilia, Trop Med Ctr, FIOCRUZ, BR-70910900 Brasilia, DF, Brazil

[22] Trop Inst Med, Mycobacteriol Unit, Dept Biomed Sci, B-2000 Antwerp, Belgium

[23] Lauro Souza Lima Inst, BR-17034971 Bauru, SP, Brazil

[24] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

瑞士国家科学基金会;

关键词：

PARA-AMINOSALICYLIC ACID; RIFAMPIN RESISTANCE; DIHYDROFOLATE-REDUCTASE; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; TUBERCULOSIS; MUTATIONS; GENE; INSIGHTS; NTH;

D O I：

10.1038/s41467-017-02576-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

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