Evolution of extensively drug-resistant tuberculosis over four decades revealed by whole genome sequencing of Mycobacterium tuberculosis from KwaZulu-Natal, South Africa

Keira A. Cohen; Thomas Abeel; Abigail Manson McGuire; Christopher A. Desjardins; Vanisha Munsamy; Terrance P. Shea; Bruce J. Walker; Nonkqubela Bantubani; Deepak V. Almeida; Lucia Alvarado; Sinead Chapman; Nomonde R. Mvelase; Eamon Y. Duffy; Michael G. Fitzgerald; Pamla Govender; Sharvari Gujja; Susanna Hamilton; Clint Howarth; Jeffrey D. Larimer; Kasmheel Maharaj; Matthew D. Pearson; Margaret E. Priest; Qiandong Zeng; Nesri Padayatchi; Jacques Grosset; Sarah K. Young; Jennifer Wortman; Koleka P. Mlisana; Max R. O'Donnell; Bruce W. Birren; William R. Bishai; Alexander S. Pym; Ashlee M. Earl

doi:10.1016/j.ijmyco.2014.11.028

Evolution of extensively drug-resistant tuberculosis over four decades revealed by whole genome sequencing of Mycobacterium tuberculosis from KwaZulu-Natal, South Africa

Keira A. Cohen, Thomas Abeel, Abigail Manson McGuire, Christopher A. Desjardins, Vanisha Munsamy, Terrance P. Shea, Bruce J. Walker, Nonkqubela Bantubani, Deepak V. Almeida, Lucia Alvarado, Sinead Chapman, Nomonde R. Mvelase, Eamon Y. Duffy, Michael G. Fitzgerald, Pamla Govender, Sharvari Gujja, Susanna Hamilton, Clint Howarth, Jeffrey D. Larimer, Kasmheel MaharajMatthew D. Pearson, Margaret E. Priest, Qiandong Zeng, Nesri Padayatchi, Jacques Grosset, Sarah K. Young, Jennifer Wortman, Koleka P. Mlisana, Max R. O'Donnell, Bruce W. Birren, William R. Bishai, Alexander S. Pym, Ashlee M. Earl

School of Medicine

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

Abstract

The largest global outbreak of extensively drug-resistant (XDR) tuberculosis (TB) was identified in Tugela Ferry, KwaZulu-Natal (KZN), South Africa in 2005. The antecedents and timing of the emergence of drug resistance in this fatal epidemic XDR outbreak are unknown, and it is unclear whether drug resistance in this region continues to be driven by clonal spread or by the development of de novo resistance. A whole genome sequencing and drug susceptibility testing (DST) was performed on 337 clinical isolates of Mycobacterium tuberculosis (M.tb) collected in KZN from 2008 to 2013, in addition to three historical isolates, one of which was isolated during the Tugela Ferry outbreak. Using a variety of whole genome comparative approaches, 11 drug-resistant clones of M.tb circulating from 2008 to 2013 were identified, including a 50-member clone of XDR M.tb that was highly related to the Tugela Ferry XDR outbreak strain. It was calculated that the evolutionary trajectory from first-line drug resistance to XDR in this clone spanned more than four decades and began at the start of the antibiotic era. It was also observed that frequent de novo evolution of MDR and XDR was present, with 56 and 9 independent evolutions, respectively. Thus, ongoing amplification of drug-resistance in KwaZulu-Natal is driven by both clonal spread and de novo acquisition of resistance. In drug-resistant TB, isoniazid resistance was overwhelmingly the initial resistance mutation to be acquired, which would not be detected by current rapid molecular diagnostics that assess only rifampicin resistance.

Original language	English (US)
Journal	International Journal of Mycobacteriology
DOIs	https://doi.org/10.1016/j.ijmyco.2014.11.028
State	Accepted/In press - 2015

Keywords

South Africa
Tuberculosis

ASJC Scopus subject areas

Infectious Diseases
Microbiology (medical)

Access to Document

10.1016/j.ijmyco.2014.11.028

Cite this

Cohen, K. A., Abeel, T., McGuire, A. M., Desjardins, C. A., Munsamy, V., Shea, T. P., Walker, B. J., Bantubani, N., Almeida, D. V., Alvarado, L., Chapman, S., Mvelase, N. R., Duffy, E. Y., Fitzgerald, M. G., Govender, P., Gujja, S., Hamilton, S., Howarth, C., Larimer, J. D., ... Earl, A. M. (Accepted/In press). Evolution of extensively drug-resistant tuberculosis over four decades revealed by whole genome sequencing of Mycobacterium tuberculosis from KwaZulu-Natal, South Africa. International Journal of Mycobacteriology. https://doi.org/10.1016/j.ijmyco.2014.11.028

Cohen, KA, Abeel, T, McGuire, AM, Desjardins, CA, Munsamy, V, Shea, TP, Walker, BJ, Bantubani, N, Almeida, DV, Alvarado, L, Chapman, S, Mvelase, NR, Duffy, EY, Fitzgerald, MG, Govender, P, Gujja, S, Hamilton, S, Howarth, C, Larimer, JD, Maharaj, K, Pearson, MD, Priest, ME, Zeng, Q, Padayatchi, N, Grosset, J, Young, SK, Wortman, J, Mlisana, KP, O'Donnell, MR, Birren, BW, Bishai, WR, Pym, AS & Earl, AM 2015, 'Evolution of extensively drug-resistant tuberculosis over four decades revealed by whole genome sequencing of Mycobacterium tuberculosis from KwaZulu-Natal, South Africa', International Journal of Mycobacteriology. https://doi.org/10.1016/j.ijmyco.2014.11.028

@article{6231c7dd26534552ae39232fd81a188e,

title = "Evolution of extensively drug-resistant tuberculosis over four decades revealed by whole genome sequencing of Mycobacterium tuberculosis from KwaZulu-Natal, South Africa",

abstract = "The largest global outbreak of extensively drug-resistant (XDR) tuberculosis (TB) was identified in Tugela Ferry, KwaZulu-Natal (KZN), South Africa in 2005. The antecedents and timing of the emergence of drug resistance in this fatal epidemic XDR outbreak are unknown, and it is unclear whether drug resistance in this region continues to be driven by clonal spread or by the development of de novo resistance. A whole genome sequencing and drug susceptibility testing (DST) was performed on 337 clinical isolates of Mycobacterium tuberculosis (M.tb) collected in KZN from 2008 to 2013, in addition to three historical isolates, one of which was isolated during the Tugela Ferry outbreak. Using a variety of whole genome comparative approaches, 11 drug-resistant clones of M.tb circulating from 2008 to 2013 were identified, including a 50-member clone of XDR M.tb that was highly related to the Tugela Ferry XDR outbreak strain. It was calculated that the evolutionary trajectory from first-line drug resistance to XDR in this clone spanned more than four decades and began at the start of the antibiotic era. It was also observed that frequent de novo evolution of MDR and XDR was present, with 56 and 9 independent evolutions, respectively. Thus, ongoing amplification of drug-resistance in KwaZulu-Natal is driven by both clonal spread and de novo acquisition of resistance. In drug-resistant TB, isoniazid resistance was overwhelmingly the initial resistance mutation to be acquired, which would not be detected by current rapid molecular diagnostics that assess only rifampicin resistance.",

keywords = "South Africa, Tuberculosis",

author = "Cohen, {Keira A.} and Thomas Abeel and McGuire, {Abigail Manson} and Desjardins, {Christopher A.} and Vanisha Munsamy and Shea, {Terrance P.} and Walker, {Bruce J.} and Nonkqubela Bantubani and Almeida, {Deepak V.} and Lucia Alvarado and Sinead Chapman and Mvelase, {Nomonde R.} and Duffy, {Eamon Y.} and Fitzgerald, {Michael G.} and Pamla Govender and Sharvari Gujja and Susanna Hamilton and Clint Howarth and Larimer, {Jeffrey D.} and Kasmheel Maharaj and Pearson, {Matthew D.} and Priest, {Margaret E.} and Qiandong Zeng and Nesri Padayatchi and Jacques Grosset and Young, {Sarah K.} and Jennifer Wortman and Mlisana, {Koleka P.} and O'Donnell, {Max R.} and Birren, {Bruce W.} and Bishai, {William R.} and Pym, {Alexander S.} and Earl, {Ashlee M.}",

year = "2015",

doi = "10.1016/j.ijmyco.2014.11.028",

language = "English (US)",

journal = "International Journal of Mycobacteriology",

issn = "2212-5531",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Evolution of extensively drug-resistant tuberculosis over four decades revealed by whole genome sequencing of Mycobacterium tuberculosis from KwaZulu-Natal, South Africa

AU - Cohen, Keira A.

AU - Abeel, Thomas

AU - McGuire, Abigail Manson

AU - Desjardins, Christopher A.

AU - Munsamy, Vanisha

AU - Shea, Terrance P.

AU - Walker, Bruce J.

AU - Bantubani, Nonkqubela

AU - Almeida, Deepak V.

AU - Alvarado, Lucia

AU - Chapman, Sinead

AU - Mvelase, Nomonde R.

AU - Duffy, Eamon Y.

AU - Fitzgerald, Michael G.

AU - Govender, Pamla

AU - Gujja, Sharvari

AU - Hamilton, Susanna

AU - Howarth, Clint

AU - Larimer, Jeffrey D.

AU - Maharaj, Kasmheel

AU - Pearson, Matthew D.

AU - Priest, Margaret E.

AU - Zeng, Qiandong

AU - Padayatchi, Nesri

AU - Grosset, Jacques

AU - Young, Sarah K.

AU - Wortman, Jennifer

AU - Mlisana, Koleka P.

AU - O'Donnell, Max R.

AU - Birren, Bruce W.

AU - Bishai, William R.

AU - Pym, Alexander S.

AU - Earl, Ashlee M.

PY - 2015

Y1 - 2015

N2 - The largest global outbreak of extensively drug-resistant (XDR) tuberculosis (TB) was identified in Tugela Ferry, KwaZulu-Natal (KZN), South Africa in 2005. The antecedents and timing of the emergence of drug resistance in this fatal epidemic XDR outbreak are unknown, and it is unclear whether drug resistance in this region continues to be driven by clonal spread or by the development of de novo resistance. A whole genome sequencing and drug susceptibility testing (DST) was performed on 337 clinical isolates of Mycobacterium tuberculosis (M.tb) collected in KZN from 2008 to 2013, in addition to three historical isolates, one of which was isolated during the Tugela Ferry outbreak. Using a variety of whole genome comparative approaches, 11 drug-resistant clones of M.tb circulating from 2008 to 2013 were identified, including a 50-member clone of XDR M.tb that was highly related to the Tugela Ferry XDR outbreak strain. It was calculated that the evolutionary trajectory from first-line drug resistance to XDR in this clone spanned more than four decades and began at the start of the antibiotic era. It was also observed that frequent de novo evolution of MDR and XDR was present, with 56 and 9 independent evolutions, respectively. Thus, ongoing amplification of drug-resistance in KwaZulu-Natal is driven by both clonal spread and de novo acquisition of resistance. In drug-resistant TB, isoniazid resistance was overwhelmingly the initial resistance mutation to be acquired, which would not be detected by current rapid molecular diagnostics that assess only rifampicin resistance.

AB - The largest global outbreak of extensively drug-resistant (XDR) tuberculosis (TB) was identified in Tugela Ferry, KwaZulu-Natal (KZN), South Africa in 2005. The antecedents and timing of the emergence of drug resistance in this fatal epidemic XDR outbreak are unknown, and it is unclear whether drug resistance in this region continues to be driven by clonal spread or by the development of de novo resistance. A whole genome sequencing and drug susceptibility testing (DST) was performed on 337 clinical isolates of Mycobacterium tuberculosis (M.tb) collected in KZN from 2008 to 2013, in addition to three historical isolates, one of which was isolated during the Tugela Ferry outbreak. Using a variety of whole genome comparative approaches, 11 drug-resistant clones of M.tb circulating from 2008 to 2013 were identified, including a 50-member clone of XDR M.tb that was highly related to the Tugela Ferry XDR outbreak strain. It was calculated that the evolutionary trajectory from first-line drug resistance to XDR in this clone spanned more than four decades and began at the start of the antibiotic era. It was also observed that frequent de novo evolution of MDR and XDR was present, with 56 and 9 independent evolutions, respectively. Thus, ongoing amplification of drug-resistance in KwaZulu-Natal is driven by both clonal spread and de novo acquisition of resistance. In drug-resistant TB, isoniazid resistance was overwhelmingly the initial resistance mutation to be acquired, which would not be detected by current rapid molecular diagnostics that assess only rifampicin resistance.

KW - South Africa

KW - Tuberculosis

UR - http://www.scopus.com/inward/record.url?scp=84921289104&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84921289104&partnerID=8YFLogxK

U2 - 10.1016/j.ijmyco.2014.11.028

DO - 10.1016/j.ijmyco.2014.11.028

M3 - Article

SN - 2212-5531

JO - International Journal of Mycobacteriology

JF - International Journal of Mycobacteriology

ER -

Evolution of extensively drug-resistant tuberculosis over four decades revealed by whole genome sequencing of Mycobacterium tuberculosis from KwaZulu-Natal, South Africa

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this