Geographic differences in the contribution of ubiA mutations to high-level ethambutol resistance in Mycobacterium tuberculosis

Subramanya Lingaraju; Leen Rigouts; Aditi Gupta; Jongseok Lee; Alaine Nyaruhirira Umubyeyi; Amy L. Davidow; Susan German; Eun Jin Cho; Ji Im Lee; Sang Nae Cho; Cheon Tae Kim; David Alland; Hassan Safi

doi:10.1128/AAC.03002-15

Geographic differences in the contribution of ubiA mutations to high-level ethambutol resistance in Mycobacterium tuberculosis

Subramanya Lingaraju, Leen Rigouts, Aditi Gupta, Jongseok Lee, Alaine Nyaruhirira Umubyeyi, Amy L. Davidow, Susan German, Eun Jin Cho, Ji Im Lee, Sang Nae Cho, Cheon Tae Kim, David Alland, Hassan Safi

Department of Microbiology

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

21 Citations (Scopus)

Abstract

Ethambutol (EMB) resistance can evolve through a multistep process, and mutations in the ubiA (Rv3806c) gene appear to be responsible for high-level EMB resistance in Mycobacterium tuberculosis. We evaluated the prevalence of ubiA and embB (Rv3795) mutations in EMB-resistant strains originating from Africa and South Korea. No differences in embB mutation frequencies were observed between strains from both origins. However, ubiA mutations were present in 45.5% ± 6.5% of the African EMB-resistant isolates but in only 9.5% ± 1.5% of the South Korean EMB-resistant isolates. The ubiA mutations associated with EMB resistance were localized to regions encoding the transmembrane domains of the protein, whereas the embB mutations were localized to regions encoding the extramembrane domains. Larger studies are needed to investigate the causes of increased ubiA mutations as a pathway to high-level EMB resistance in African countries, such as extended EMB usage during tuberculosis treatment.

Original language	English
Pages (from-to)	4101-4105
Number of pages	5
Journal	Antimicrobial agents and chemotherapy
Volume	60
Issue number	7
DOIs	https://doi.org/10.1128/AAC.03002-15
Publication status	Published - 2016 Jul

Bibliographical note

Funding Information:
This work was supported in part by National Institutes of Health grant AI080653 and the South Korean Ministry of Health and Welfare. We gratefully acknowledged the WHO TDR Tuberculosis Strain Bank for the strains and the National Masan Hospital in Changwon, South Korea, and the National Reference Laboratory in Rwanda for clinical DNA samples. This work, including the efforts of David Alland, was funded by HHS | National Institutes of Health (NIH) (AI080653).

Publisher Copyright:
Copyright © 2016, American Society for Microbiology. All Rights Reserved.

All Science Journal Classification (ASJC) codes

Pharmacology
Pharmacology (medical)
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1128/AAC.03002-15

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Lingaraju, S., Rigouts, L., Gupta, A., Lee, J., Umubyeyi, A. N., Davidow, A. L., German, S., Cho, E. J., Lee, J. I., Cho, S. N., Kim, C. T., Alland, D., & Safi, H. (2016). Geographic differences in the contribution of ubiA mutations to high-level ethambutol resistance in Mycobacterium tuberculosis. Antimicrobial agents and chemotherapy, 60(7), 4101-4105. https://doi.org/10.1128/AAC.03002-15

@article{8a3eb239c0784596b8bd60989da15f31,

title = "Geographic differences in the contribution of ubiA mutations to high-level ethambutol resistance in Mycobacterium tuberculosis",

abstract = "Ethambutol (EMB) resistance can evolve through a multistep process, and mutations in the ubiA (Rv3806c) gene appear to be responsible for high-level EMB resistance in Mycobacterium tuberculosis. We evaluated the prevalence of ubiA and embB (Rv3795) mutations in EMB-resistant strains originating from Africa and South Korea. No differences in embB mutation frequencies were observed between strains from both origins. However, ubiA mutations were present in 45.5% ± 6.5% of the African EMB-resistant isolates but in only 9.5% ± 1.5% of the South Korean EMB-resistant isolates. The ubiA mutations associated with EMB resistance were localized to regions encoding the transmembrane domains of the protein, whereas the embB mutations were localized to regions encoding the extramembrane domains. Larger studies are needed to investigate the causes of increased ubiA mutations as a pathway to high-level EMB resistance in African countries, such as extended EMB usage during tuberculosis treatment.",

author = "Subramanya Lingaraju and Leen Rigouts and Aditi Gupta and Jongseok Lee and Umubyeyi, {Alaine Nyaruhirira} and Davidow, {Amy L.} and Susan German and Cho, {Eun Jin} and Lee, {Ji Im} and Cho, {Sang Nae} and Kim, {Cheon Tae} and David Alland and Hassan Safi",

note = "Funding Information: This work was supported in part by National Institutes of Health grant AI080653 and the South Korean Ministry of Health and Welfare. We gratefully acknowledged the WHO TDR Tuberculosis Strain Bank for the strains and the National Masan Hospital in Changwon, South Korea, and the National Reference Laboratory in Rwanda for clinical DNA samples. This work, including the efforts of David Alland, was funded by HHS | National Institutes of Health (NIH) (AI080653). Publisher Copyright: Copyright {\textcopyright} 2016, American Society for Microbiology. All Rights Reserved.",

year = "2016",

month = jul,

doi = "10.1128/AAC.03002-15",

language = "English",

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Lingaraju, S, Rigouts, L, Gupta, A, Lee, J, Umubyeyi, AN, Davidow, AL, German, S, Cho, EJ, Lee, JI, Cho, SN, Kim, CT, Alland, D & Safi, H 2016, 'Geographic differences in the contribution of ubiA mutations to high-level ethambutol resistance in Mycobacterium tuberculosis', Antimicrobial agents and chemotherapy, vol. 60, no. 7, pp. 4101-4105. https://doi.org/10.1128/AAC.03002-15

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T1 - Geographic differences in the contribution of ubiA mutations to high-level ethambutol resistance in Mycobacterium tuberculosis

AU - Lingaraju, Subramanya

AU - Rigouts, Leen

AU - Gupta, Aditi

AU - Lee, Jongseok

AU - Umubyeyi, Alaine Nyaruhirira

AU - Davidow, Amy L.

AU - German, Susan

AU - Cho, Eun Jin

AU - Lee, Ji Im

AU - Cho, Sang Nae

AU - Kim, Cheon Tae

AU - Alland, David

AU - Safi, Hassan

N1 - Funding Information: This work was supported in part by National Institutes of Health grant AI080653 and the South Korean Ministry of Health and Welfare. We gratefully acknowledged the WHO TDR Tuberculosis Strain Bank for the strains and the National Masan Hospital in Changwon, South Korea, and the National Reference Laboratory in Rwanda for clinical DNA samples. This work, including the efforts of David Alland, was funded by HHS | National Institutes of Health (NIH) (AI080653). Publisher Copyright: Copyright © 2016, American Society for Microbiology. All Rights Reserved.

PY - 2016/7

Y1 - 2016/7

N2 - Ethambutol (EMB) resistance can evolve through a multistep process, and mutations in the ubiA (Rv3806c) gene appear to be responsible for high-level EMB resistance in Mycobacterium tuberculosis. We evaluated the prevalence of ubiA and embB (Rv3795) mutations in EMB-resistant strains originating from Africa and South Korea. No differences in embB mutation frequencies were observed between strains from both origins. However, ubiA mutations were present in 45.5% ± 6.5% of the African EMB-resistant isolates but in only 9.5% ± 1.5% of the South Korean EMB-resistant isolates. The ubiA mutations associated with EMB resistance were localized to regions encoding the transmembrane domains of the protein, whereas the embB mutations were localized to regions encoding the extramembrane domains. Larger studies are needed to investigate the causes of increased ubiA mutations as a pathway to high-level EMB resistance in African countries, such as extended EMB usage during tuberculosis treatment.

AB - Ethambutol (EMB) resistance can evolve through a multistep process, and mutations in the ubiA (Rv3806c) gene appear to be responsible for high-level EMB resistance in Mycobacterium tuberculosis. We evaluated the prevalence of ubiA and embB (Rv3795) mutations in EMB-resistant strains originating from Africa and South Korea. No differences in embB mutation frequencies were observed between strains from both origins. However, ubiA mutations were present in 45.5% ± 6.5% of the African EMB-resistant isolates but in only 9.5% ± 1.5% of the South Korean EMB-resistant isolates. The ubiA mutations associated with EMB resistance were localized to regions encoding the transmembrane domains of the protein, whereas the embB mutations were localized to regions encoding the extramembrane domains. Larger studies are needed to investigate the causes of increased ubiA mutations as a pathway to high-level EMB resistance in African countries, such as extended EMB usage during tuberculosis treatment.

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Geographic differences in the contribution of ubiA mutations to high-level ethambutol resistance in Mycobacterium tuberculosis

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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