Extended Data Fig. 10: The antidote benzbromarone selectively protects Bacteroides species from erythromycin in microbial communities.
From: Unravelling the collateral damage of antibiotics on gut bacteria
a. The same 7-member synthetic gut microbial community as in Fig. 3a can be protected from erythromycin by the antidote benzbromarone. Heatmaps depict median bacterial growth based on normalized AUCs of the community of three replicates. b. Community compositions in selected erythromycin-benzbromarone concentration combinations (1–4 referring to checkerboard tiles in a) demonstrate that benzbromarone 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. c. When the Bacteroidales community contains the pathogen E. faecalis, benzbromarone rescues community growth upon erythromycin treatment, but enhances the ability of erythromycin to target E. faecalis. Plotted as in Fig. 3c. d–f. In complex human-stool derived communities from nine healthy donors (column #1 – 9), benzbromarone protects 65% of Bacteroidales OTUs from erythromycin, and at least one sensitive Bacteroidales OTU per individual (2 biological × 2 technical replicates). Plotted as in Fig. 3d. The fractions of rescued OTUs per order (e) and for Bacteroidales OTUs per genus (f) across all nine donors indicate that primarily Bacteroides species are rescued. g. In gnotobiotic mice colonized with a defined 12-member mouse microbiome31 and B. vulgatus, administration of benzbromarone slightly (albeit not significantly, two-sided Mann-Whitney U test) mitigates the temporal decrease in fecal B. vulgatus counts that erythromycin causes. Mice received a single oral dose of erythromycin (N = 9) or erythromycin + benzbromarone (N = 9) in two independent experiments. Data of the erythromycin-treated group is partially overlapping with data shown in Fig. 3g as experiments were conducted in parallel. Boxes are plotted as in Fig. 1c. h. Both groups of mice show similar faecal erythromycin concentrations over the course of the experiment shown in g.
