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

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21 Citations (Scopus)


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 languageEnglish
Pages (from-to)4101-4105
Number of pages5
JournalAntimicrobial agents and chemotherapy
Issue number7
Publication statusPublished - 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


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