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. 2020 May 3;11(7):505–517. doi: 10.1007/s13238-020-00726-6

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Mapping of ethambutol-resistant mutation sites. (A) Log-Scaled histogram of the occurrence of the top 30 frequent ethambutol-resistant mutations in EmbB in 61 studies collected from the drug-resistance database, MycoResistance, and their positions on the DPA-bound EmbB structure, most notably around DPA binding cavity. Mutations with more than 20 occurrences are colored in yellow, and those with more than 1,000 occurrences are in red. (B) MST assays for the binding of ethambutol to wild-type EmbB treated with 2× MIC of BTZ-043 or inhibitor-free during culture and ethambutol resistant mutation hotspot M292L represented by red sphere in (A). Error bars represent mean ± SEM based on three independent measurements. Binding curves and K_D values are also shown. See also Figs. S7 and S8