Ethambutol (EMB) resistance can evolve through a multi-step process, and mutations in the ubiA (Rv3806c) gene appear to be responsible for high-level EMB-resistance in M. 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 the trans-membrane domains of the encoded protein, whereas the embB mutations are localized in the extra-membrane 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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