High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance
Fig 5
The combination of disrupted nucleotide balance and premature DNA chain termination act synergistically to inhibit E. coli growth.
Bars for nonsynergistic combinations (fractional inhibitory concentration index [FICI] > 0.5) are colored blue, and bars for synergistic combinations (FICI ≤ 0.5) are colored yellow. Checkerboard assays for (A) nucleotide homeostasis disruptors + azidothymidine (AZT) or trimethoprim and (B) Nucleoside analogs + AZT or trimethoprim show synergy between nucleotide homeostasis inhibitors and AZT or nucleoside analogs and trimethoprim but not the reverse. (C) Growth of wild-type and mutant cells on AZT, trimethoprim (TMP) or rifampicin (RIF). These data are the average of 3 replicates. The data for parts A and B are in S9 Table. The data for part C are in S10 Table.