Figure 2.

Affected codon positions in Rv0678 leading to bedaquiline resistance in this study and in clinical strains

(A) The codon positions in Rv0678 that conferred bedaquiline resistance (and borderline resistance) were compared between three datasets: in-vitro selected mutants, which were single clones isolated from in-vitro evolution experiments (appendix 3 [p 1]); in-vitro population sequencing, corresponding to variants detected from deep sequencing of the entire mutant population in in-vitro evolution experiments (appendix 3 [p 2]); and variants in clinical strains from the CRyPTIC project and literature-reported strains (appendix 2). The variant at base-pair position –10 is the variant in the promoter region. In-vitro population sequencing was not quantifiable by number of isolates, hence the negative bar orientation for the affected codon positions. (B) The Venn diagram shows the number of overlapping codon positions where a mutation was detected between the three datasets. CRyPTIC=Comprehensive Resistance Prediction for Tuberculosis: an International Consortium.