Fig. 2: Bedaquiline potentiates reactive oxygen species formation in cells with deficient catalase activity.

a H37Rv ∆katG cells are hypersensitive to H₂O₂ relative to wild-type cells in 8-day growth inhibition dose-response experiments. katG complementation reduces H₂O₂ sensitivity in ∆katG cells. n = 3 biological replicates for H37Rv and ∆katG. n = 2 biological replicates for ∆katG:pkatG. b MDR and non-MDR INH-resistant clinical strains are hypersensitive to H₂O₂ relative to INH-susceptible clinical strains in 8-day growth inhibition dose-response experiments. n = 4 biological replicates for non-MDR INH-resistant TDR-TB-42 (red). n = 1 biological replicate for all other TDR-TB clinical strains. Error bars for INH-susceptible and MDR clinical strains computed across INH-susceptible and MDR clinical strains, respectively. c BDQ treatment increases devR, katG, and oxyS expression in wild-type H37Rv cells as measured by RNA sequencing. Expression data reported as smooth quantile normalized log₂ sequencing counts. n = 3 biological replicates. d KatG-deficient mc²8245 cells are hypersensitive to BDQ relative to KatG-replete mc²7902 cells in 8-day growth inhibition dose-response experiments. n = 2 biological replicates for mc²7902 and n = 3 biological replicates for mc²8245. e Left: BDQ induces ROS accumulation in mc²7902 and mc²8245 cells as reported by CellROX fluorescence over 4 days treatment with 0.68 μg/mL BDQ. Right: ROS accumulation was further enhanced in mc²8245 cells than in mc²7902 cells. n = 3 biological replicates. p = 0.0279 as determined by two-sided Welch’s t-test. Error bars depict standard errors of the mean after error propagation. f Protein carbonylation is potentiated in mc²8245 cells relative to mc²7902 cells after 16 hours treatment with 2.7 μg/mL BDQ as reported by ELISA. n = 3 biological replicates. g Deoxyguanosine oxidation is potentiated in mc²8245 relative to mc²7902 cells after 16 hours treatment with 2.7 μg/mL BDQ as reported by ELISA. n = 3 biological replicates. Brown-Forsythe and Welch ANOVA statistical tests were performed on RNA expression, CellROX, protein carbonylation, and deoxyguanosine oxidation experiments, with comparisons between BDQ-treated and untreated cells wild-type and ∆katG cells or between untreated wild-type and ∆katG as indicated with FDR correction. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001. Data depicted as mean ± SEM. Source data are provided in the Source Data file.