Extended Data Figure 11. The antidote tolfenamic acid protects Bacteroides species from erythromycin in microbial communities.

a. Tolfenamic acid rescues commensal growth (based on median AUCs, N=2) at clinical relevant erythromycin concentrations in a concentration-dependent manner (anaerobic conditions). Erythromycin still retains its activity against pertinent pathogens such as E. faecium, E. faecalis (based on median AUCs, N=3, anaerobic conditions) and S. aureus ([erythromycin]=0.14 μM, N=3, aerobic conditions). Error bars depict standard deviation.

b. The same 7-member synthetic gut microbial community as in Fig. 3a can be protected from erythromycin by the tolfenamic acid. Heat maps depict median bacterial growth based on normalized AUCs of the community of 3 replicates.

c. Community compositions in selected erythromycin-tolfenamic acid concentration combinations (1-4 referring to checkerboard tiles in b) demonstrate that tolfenamic acid alone does not alter the community structure, but rescues some Bacteroides species and largely the community composition from erythromycin treatment. Depicted as in Fig. 3b – control and erythromycin alone experiments same as in Fig. 3b.

d-f. In complex human-stool derived communities from 9 healthy donors (column #1 – 9), tolfenamic acid can rescue 42% of the erythromycin-sensitive Bacteroidales OTUs (2 biological X 2 technical replicates). Data is plotted as in Fig. 3d. Bars depict the absolute numbers of erythromycin-sensitive OTUs and the percentage of rescued OTUs per order (e) or genus (f) across all nine individuals.