Fig. 1.

C10 blocks hypoxia-induced tolerance to H₂O₂ and INH. (A) The bicyclic 2-pyridone scaffold shared by all compounds in the screening library in which compounds contained different substituents at each of the “R” groups. (B) The chemical structure of C10. (C) Mtb was incubated in low oxygen in Sauton’s medium in the presence of DMSO or 50 μM C10 for 3 wk, then reaerated and incubated for an additional 2 wk. Representative pictures from three independent experiments are shown. (D) Mtb ± 50 μM C10 was treated the same as the cultures in C, and viable cfu/mL were enumerated at 5 wk. n = 3. ns, not significant by unpaired t test. (E) Schematic of stress assays. (F and G) Mtb was cultured in low oxygen conditions ± 50 μM C10 for 3 wk, then reaerated and treated with H₂O₂ (F) or INH (G) for an additional 2 wk before cfu/mL were enumerated. Mean ± SEM between biological triplicates is graphed for each sample. ND, not detected; limit of detection, 67 cfu/mL. Complete statistical comparisons for all data are provided in SI Appendix, Table S1.