Extended Data Fig. 1: Bacterial taxa vary in their sensitivity to fluoropyrimidines despite the rapid emergence of resistance during in vitro growth.
From: Host and gut bacteria share metabolic pathways for anti-cancer drug metabolism
(a) Simplified metabolic pathway for the bioactivation of the oral prodrug capecitabine (CAP) to 5-fluorouracil (5-FU), 5-fluorodeoxyuridine (FUDR), and downstream metabolites1. Red indicates chemical groups hydrolyzed during the conversion of CAP to 5-FU. Sequential reactions are indicated by multiple arrows. (b,c) Variation in (b) 5-FU and (c) FUDR minimal inhibitory concentration (MIC) at the phylum level. Bacterial strains where no MIC could be determined were set to the maximum tested concentration. Each dot represents a bacterial isolate. Red lines indicate the median. p-values, Kruskal-Wallis test with Dunn’s correction for multiple comparisons. (d) 5-FU MICs of parent and 5-FU-resistant strains of E. coli MG1655, B. fragilis DSM2151, and B. ovatus DSM1896 (see Supplementary Table 2). The type of selection is indicated by the strain identifier: A = agar; L = liquid. (e) Wild-type E. coli BW25113 was assayed for conversion of CAP to 5-FU by LC-MS/MS (n = 3 biological replicates per group). Open circles represent individual values, filled circles represent mean values. p-values, two-tailed paired t test comparing final vs. baseline values for each analyte.
