Extended Data Fig. 7. Effects of propionate and vitamin B₁₂ supplementation on MMCoA and propionyl-CoA metabolic pathways in Mtb.

a, Abundance of metabolites in propionyl-CoA and MMCoA metabolism in PDIM(+) Mtb H37Rv wildtype grown in standard 7H9/OADC/glycerol/tyloxapol media and supplemented with propionate or vitamin B₁₂, and b, in PDIM(+) and PDIM(-) H37Rv grown in 7H9/OADC/glycerol/tyloxapol ± 0.1 mM propionate. Abundances are shown as normalized area under the curve (AUC) (see Methods). Mean ± SD for n = 6 biological replicates from two independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; one-way ANOVA with Tukey’s multiple comparison test. Significant differences compared to unsupplemented media are indicated in (a), and between ± propionate for each strain and between strains for each condition in (b). PROP, propionate; PROP-CoA, propionyl-CoA; MMCoA, methylmalonyl-CoA; SUC-CoA, succinyl-CoA; SUC, succinate; 2MC/2MIC, 2-methyl(iso)citrate; and PYR, pyruvate. Succinyl-CoA and methyl(iso)citrate were not able to be detected in samples by our method. Propionyl-CoA was close to the detection limit and was not detected in all samples (n.d. = not detected). The data for MMCoA are also shown in Fig. 3d,e. See also Supplementary Fig. 8.