Figure 3. Bioenergetic analysis of Mtb H37Rv, cytochrome bd knockout (cydKO), and cydKO strain with Q203 resistance SNP (A317V) to ETC drugs.

At indicated times, 2 g l⁻¹ glucose was added, followed by either Q203, BDQ, or DCCD, followed by 2 μM CCCP. (a) 300 × MIC₅₀ BDQ treatment has a very similar effect on H37Rv and cydKO. (b) 300 × MIC₅₀ Q203 treatment causes H37Rv OCR to increase, however cydKO OCR drops to zero, while A317V OCR is unchanged. The untreated media OCR profiles of the Mtb H37Rv, cydKO and A317V strains are provided in Supplementary Fig. 4. (c) 100 μM of the ATP synthase inhibitor DCCD causes a similar OCR increase to 30 × MIC₅₀ BDQ, although somewhat less in magnitude at these concentrations. (d) H37Rv Mtb was cultured for 24 h with 30 × MIC₅₀ of BDQ, Q203, CFZ, a RIF/INH combination, or media control. Relative abundance of ATP, ADP, and AMP was measured by LC-MS/MS. Standard deviations of three technical replicates are shown, all experiments were performed at least twice. *P<0.05, **P<0.005 and ****P<0.0001 (one-way analysis of variance using GraphPad Prism 6.05).