Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance

Abigail L. Manson; Keira A. Cohen; Thomas Abeel; Christopher A. Desjardins; Derek T. Armstrong; Clifton E. Barry; Jeannette Brand; Sinéad B. Chapman; Sang Nae Cho; Andrei Gabrielian; James Gomez; Andreea M. Jodals; Moses Joloba; Pontus Jureen; Jong Seok Lee; Lesibana Malinga; Mamoudou Maiga; Dale Nordenberg; Ecaterina Noroc; Elena Romancenco; Alex Salazar; Willy Ssengooba; A. A. Velayati; Kathryn Winglee; Aksana Zalutskaya; Laura E. Via; Gail H. Cassell; Susan E. Dorman; Jerrold Ellner; Parissa Farnia; James E. Galagan; Alex Rosenthal; Valeriu Crudu; Daniela Homorodean; Po Ren Hsueh; Sujatha Narayanan; Alexander S. Pym; Alena Skrahina; Soumya Swaminathan; Martie Van Der Walt; David Alland; William R. Bishai; Ted Cohen; Sven Hoffner; Bruce W. Birren; Ashlee M. Earl

doi:10.1038/ng.3767

Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance

Abigail L. Manson, Keira A. Cohen, Thomas Abeel, Christopher A. Desjardins, Derek T. Armstrong, Clifton E. Barry, Jeannette Brand, Sinéad B. Chapman, Sang Nae Cho, Andrei Gabrielian, James Gomez, Andreea M. Jodals, Moses Joloba, Pontus Jureen, Jong Seok Lee, Lesibana Malinga, Mamoudou Maiga, Dale Nordenberg, Ecaterina Noroc, Elena RomancencoAlex Salazar, Willy Ssengooba, A. A. Velayati, Kathryn Winglee, Aksana Zalutskaya, Laura E. Via, Gail H. Cassell, Susan E. Dorman, Jerrold Ellner, Parissa Farnia, James E. Galagan, Alex Rosenthal, Valeriu Crudu, Daniela Homorodean, Po Ren Hsueh, Sujatha Narayanan, Alexander S. Pym, Alena Skrahina, Soumya Swaminathan, Martie Van Der Walt, David Alland, William R. Bishai, Ted Cohen, Sven Hoffner, Bruce W. Birren, Ashlee M. Earl

Research output: Contribution to journal › Article › peer-review

197 Scopus citations

Abstract

Multidrug-resistant tuberculosis (MDR-TB), caused by drug-resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. Here we examined a data set of whole-genome sequences from 5,310 M. tuberculosis isolates from five continents. Despite the great diversity of these isolates with respect to geographical point of isolation, genetic background and drug resistance, the patterns for the emergence of drug resistance were conserved globally. We have identified harbinger mutations that often precede multidrug resistance. In particular, the katG mutation encoding p.Ser315Thr, which confers resistance to isoniazid, overwhelmingly arose before mutations that conferred rifampicin resistance across all of the lineages, geographical regions and time periods. Therefore, molecular diagnostics that include markers for rifampicin resistance alone will be insufficient to identify pre-MDR strains. Incorporating knowledge of polymorphisms that occur before the emergence of multidrug resistance, particularly katG p.Ser315Thr, into molecular diagnostics should enable targeted treatment of patients with pre-MDR-TB to prevent further development of MDR-TB.

Original language	English (US)
Pages (from-to)	395-402
Number of pages	8
Journal	Nature genetics
Volume	49
Issue number	3
DOIs	https://doi.org/10.1038/ng.3767
State	Published - Mar 1 2017
Externally published	Yes

All Science Journal Classification (ASJC) codes

Genetics

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10.1038/ng.3767

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Manson, A. L., Cohen, K. A., Abeel, T., Desjardins, C. A., Armstrong, D. T., Barry, C. E., Brand, J., Chapman, S. B., Cho, S. N., Gabrielian, A., Gomez, J., Jodals, A. M., Joloba, M., Jureen, P., Lee, J. S., Malinga, L., Maiga, M., Nordenberg, D., Noroc, E., ... Earl, A. M. (2017). Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance. Nature genetics, 49(3), 395-402. https://doi.org/10.1038/ng.3767

@article{ed423c64908142899d747de3f60731c0,

title = "Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance",

abstract = "Multidrug-resistant tuberculosis (MDR-TB), caused by drug-resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. Here we examined a data set of whole-genome sequences from 5,310 M. tuberculosis isolates from five continents. Despite the great diversity of these isolates with respect to geographical point of isolation, genetic background and drug resistance, the patterns for the emergence of drug resistance were conserved globally. We have identified harbinger mutations that often precede multidrug resistance. In particular, the katG mutation encoding p.Ser315Thr, which confers resistance to isoniazid, overwhelmingly arose before mutations that conferred rifampicin resistance across all of the lineages, geographical regions and time periods. Therefore, molecular diagnostics that include markers for rifampicin resistance alone will be insufficient to identify pre-MDR strains. Incorporating knowledge of polymorphisms that occur before the emergence of multidrug resistance, particularly katG p.Ser315Thr, into molecular diagnostics should enable targeted treatment of patients with pre-MDR-TB to prevent further development of MDR-TB.",

author = "Manson, {Abigail L.} and Cohen, {Keira A.} and Thomas Abeel and Desjardins, {Christopher A.} and Armstrong, {Derek T.} and Barry, {Clifton E.} and Jeannette Brand and Chapman, {Sin{\'e}ad B.} and Cho, {Sang Nae} and Andrei Gabrielian and James Gomez and Jodals, {Andreea M.} and Moses Joloba and Pontus Jureen and Lee, {Jong Seok} and Lesibana Malinga and Mamoudou Maiga and Dale Nordenberg and Ecaterina Noroc and Elena Romancenco and Alex Salazar and Willy Ssengooba and Velayati, {A. A.} and Kathryn Winglee and Aksana Zalutskaya and Via, {Laura E.} and Cassell, {Gail H.} and Dorman, {Susan E.} and Jerrold Ellner and Parissa Farnia and Galagan, {James E.} and Alex Rosenthal and Valeriu Crudu and Daniela Homorodean and Hsueh, {Po Ren} and Sujatha Narayanan and Pym, {Alexander S.} and Alena Skrahina and Soumya Swaminathan and {Van Der Walt}, Martie and David Alland and Bishai, {William R.} and Ted Cohen and Sven Hoffner and Birren, {Bruce W.} and Earl, {Ashlee M.}",

year = "2017",

month = mar,

day = "1",

doi = "10.1038/ng.3767",

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volume = "49",

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Manson, AL, Cohen, KA, Abeel, T, Desjardins, CA, Armstrong, DT, Barry, CE, Brand, J, Chapman, SB, Cho, SN, Gabrielian, A, Gomez, J, Jodals, AM, Joloba, M, Jureen, P, Lee, JS, Malinga, L, Maiga, M, Nordenberg, D, Noroc, E, Romancenco, E, Salazar, A, Ssengooba, W, Velayati, AA, Winglee, K, Zalutskaya, A, Via, LE, Cassell, GH, Dorman, SE, Ellner, J, Farnia, P, Galagan, JE, Rosenthal, A, Crudu, V, Homorodean, D, Hsueh, PR, Narayanan, S, Pym, AS, Skrahina, A, Swaminathan, S, Van Der Walt, M, Alland, D, Bishai, WR, Cohen, T, Hoffner, S, Birren, BW & Earl, AM 2017, 'Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance', Nature genetics, vol. 49, no. 3, pp. 395-402. https://doi.org/10.1038/ng.3767

TY - JOUR

T1 - Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance

AU - Manson, Abigail L.

AU - Cohen, Keira A.

AU - Abeel, Thomas

AU - Desjardins, Christopher A.

AU - Armstrong, Derek T.

AU - Barry, Clifton E.

AU - Brand, Jeannette

AU - Chapman, Sinéad B.

AU - Cho, Sang Nae

AU - Gabrielian, Andrei

AU - Gomez, James

AU - Jodals, Andreea M.

AU - Joloba, Moses

AU - Jureen, Pontus

AU - Lee, Jong Seok

AU - Malinga, Lesibana

AU - Maiga, Mamoudou

AU - Nordenberg, Dale

AU - Noroc, Ecaterina

AU - Romancenco, Elena

AU - Salazar, Alex

AU - Ssengooba, Willy

AU - Velayati, A. A.

AU - Winglee, Kathryn

AU - Zalutskaya, Aksana

AU - Via, Laura E.

AU - Cassell, Gail H.

AU - Dorman, Susan E.

AU - Ellner, Jerrold

AU - Farnia, Parissa

AU - Galagan, James E.

AU - Rosenthal, Alex

AU - Crudu, Valeriu

AU - Homorodean, Daniela

AU - Hsueh, Po Ren

AU - Narayanan, Sujatha

AU - Pym, Alexander S.

AU - Skrahina, Alena

AU - Swaminathan, Soumya

AU - Van Der Walt, Martie

AU - Alland, David

AU - Bishai, William R.

AU - Cohen, Ted

AU - Hoffner, Sven

AU - Birren, Bruce W.

AU - Earl, Ashlee M.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Multidrug-resistant tuberculosis (MDR-TB), caused by drug-resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. Here we examined a data set of whole-genome sequences from 5,310 M. tuberculosis isolates from five continents. Despite the great diversity of these isolates with respect to geographical point of isolation, genetic background and drug resistance, the patterns for the emergence of drug resistance were conserved globally. We have identified harbinger mutations that often precede multidrug resistance. In particular, the katG mutation encoding p.Ser315Thr, which confers resistance to isoniazid, overwhelmingly arose before mutations that conferred rifampicin resistance across all of the lineages, geographical regions and time periods. Therefore, molecular diagnostics that include markers for rifampicin resistance alone will be insufficient to identify pre-MDR strains. Incorporating knowledge of polymorphisms that occur before the emergence of multidrug resistance, particularly katG p.Ser315Thr, into molecular diagnostics should enable targeted treatment of patients with pre-MDR-TB to prevent further development of MDR-TB.

AB - Multidrug-resistant tuberculosis (MDR-TB), caused by drug-resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. Here we examined a data set of whole-genome sequences from 5,310 M. tuberculosis isolates from five continents. Despite the great diversity of these isolates with respect to geographical point of isolation, genetic background and drug resistance, the patterns for the emergence of drug resistance were conserved globally. We have identified harbinger mutations that often precede multidrug resistance. In particular, the katG mutation encoding p.Ser315Thr, which confers resistance to isoniazid, overwhelmingly arose before mutations that conferred rifampicin resistance across all of the lineages, geographical regions and time periods. Therefore, molecular diagnostics that include markers for rifampicin resistance alone will be insufficient to identify pre-MDR strains. Incorporating knowledge of polymorphisms that occur before the emergence of multidrug resistance, particularly katG p.Ser315Thr, into molecular diagnostics should enable targeted treatment of patients with pre-MDR-TB to prevent further development of MDR-TB.

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U2 - 10.1038/ng.3767

DO - 10.1038/ng.3767

M3 - Article

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SN - 1061-4036

VL - 49

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EP - 402

JO - Nature genetics

JF - Nature genetics

IS - 3

ER -

Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance

Abstract

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