Extended Data Fig. 10: Ticagrelor affects purine and teichoic acid biosynthesis.

a, KEGG enrichment of hits at 5% FDR from whole-cell or lysate samples. Only sets yielding significant enrichments (whole-cell down- and up-regulation, and lysate stabilization) are shown (Supplementary Table 7). The first 15 terms in order of significance are shown. The dashed lines mark the enrichment significance cut-off (adjusted p-value < 0.05, one-sided Fisher’s exact test). The number of protein hits is annotated for each term. b, Thermal stability profiles of members of the purine biosynthesis pathway. Protein fold change is shown for each temperature and ticagrelor concentration. c, Chemical structure of ticagrelor. d, Growth (endpoint OD_595nm after 11 h, corresponding to the beginning of stationary phase for the untreated control, Methods) measured in the presence of serial two-fold dilutions of ticagrelor in presence or absence of purines at the indicated concentration, normalised by no-drug controls, in S. aureus Newman in SSM9PR-defined medium (mean across four biological replicates; error bars represent standard error; Methods). e, Ticagrelor synergizes with nisin in vitro (median fitness across two biological replicates, results obtained as in Fig. 2d, Supplementary File). f, Thermal stability profiles of proteins involved in teichoic acid biosynthesis, represented as in b. g, Growth (endpoint OD_595nm, corresponding to the beginning of stationary phase for the control strain MM76, Methods, Supplementary File) measured in the presence of serial two-fold dilutions of nisin, normalised by no-drug controls, in the S. aureus IPTG-inducible knockdown mutants dltABCD and tagG and their control strain MM76 (Methods), in presence or absence of 500 µM IPTG to induce maximal knockdown of the gene targeted (mean across four biological replicates; error bars represent standard error). All strains are grown in presence of 5 µg/ml erythromycin and 10 µg/ml chloramphenicol to maintain the CRISPRi plasmids⁷⁶ (Methods). For all controls and full growth curves see Supplementary File. h, Raw data (OD_410nm) from Fig. 5g are shown alongside all controls (samples not incubated with 250 µg/ml cytochrome c, cytochrome c standard curve including buffer control). The linear fit for the cytochrome c standard curve used to infer the unbound cytochrome C fraction in supernatants is shown (n = 4, mean and standard error of the mean are shown. Data points represent reads (n = 4 biological replicates for each condition, Methods).