Fig. 3: BDQ exposure induces the TCA cycle to progress via the glyoxylate shunt. | Nature Communications

Fig. 3: BDQ exposure induces the TCA cycle to progress via the glyoxylate shunt.

From: Bedaquiline reprograms central metabolism to reveal glycolytic vulnerability in Mycobacterium tuberculosis

Fig. 3: BDQ exposure induces the TCA cycle to progress via the glyoxylate shunt.The alternative text for this image may have been generated using AI.

a The TCA cycle can progress via the oxidative branch, (b) the glyoxylate shunt or (c) via the MCC. d To investigate the effect of BDQ on gluconeogenesis and the catalytic direction of PEPCK, we cultured Mtb cells in the presence of glucose or acetate and 13CO2 (labelled NaH13CO3) as the tracer. Notably, there is more labelled (e) isocitrate (IC), (g) succinate and (h) malate and less (f) αKG. However, (i) phosphoenolpyruvate (PEP) levels increase following BDQ treatment in acetate conditions, with (j) no M + 1 glyceraldehyde-3-phosphate (G3P) or (k) fructose-6-phosphate (F6P) being detected after BDQ treatment (under acetate conditions). Mean + /− standard error of the mean (SEM) of at least three replicate extracts is indicated. One representative experiment is shown, with the experiment being repeated a minimum of two times. A two-way ANOVA and a Tukey multiple-comparison test were used for the statistical analysis. n = 4 biologically independent samples. *P < 0.05, **P < 0.01, ***P < 0.001. BDQ - bedaquiline, nd - not detected.

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