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. 2022 Jun 7;13:3165. doi: 10.1038/s41467-022-30967-4

Fig. 6. Modulation of purine metabolism affects (p)ppGpp and ATP synthesis and is linked to changes in ABX sensitivity.

Fig. 6

a Key steps in purine metabolism with the same color coding as in Fig. 3. SP_1097 is listed as well, for which we found no change in ABX sensitivity, which is denoted with ‘np’ for no phenotype. The putative deoxyribose transporter (SP_0845-0848), a high-connectivity cluster in Fig. 2, is also shown. b Single knockouts for deoB/SP_0829 and SP_0846, as well as a double knockout show that mutants and WT grow equally well in the absence of antibiotics. In the presence of Synercid, as predicted and indicated by their ABX sensitivity bar, the single knockouts display a higher sensitivity to the drug then the WT. The double mutant suppresses the increased Synercid sensitivity phenotype of the single mutants, indicating that the positive interaction that is found in the co-fitness network leads to a positive genetic interaction between these genes. c Single and double knockouts of SP_1097 and SP_1645/relA grow just as well as WT in the absence of antibiotics. As predicted SP_1097 is equally sensitive to cefepime as the WT, while ΔrelA has decreased sensitivity as indicated by its ABX sensitivity bar in a. Additionally, the double knockout has decreased sensitivity to cefepime, indicating the dominant phenotype of ΔrelA. d The phenotype of ΔSP_0831 was validated in growth as well, showing no change in growth in the absence of ABX, and decreased sensitivity (i.e., increased relative growth) in the presence of cefepime (FEP). e The alarmone (p)ppGpp is below the limit of detection (b.l.d.) in the absence of stress, upon induction with mupirocin it is synthesized in equal amounts in WT, ΔSP_0831 and ΔSP_1097, while it cannot be synthesized when relA is absent. f Synthesis of di- and trinucleotides is significantly affected in the different mutants upon mupirocin exposure. Mean values ± SEM are shown from n≥3 independent experiments. Significance is measured through a paired t-test with an FDR adjusted p value for multiple comparisons: *p < 0.05, **p < 0.01, ***p < 0.001, ns not significant. Source data are provided as a Source Data file.