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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13 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 languageEnglish
Pages (from-to)4101-4105
Number of pages5
JournalAntimicrobial agents and chemotherapy
Volume60
Issue number7
DOIs
Publication statusPublished - 2016 Jul

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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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