Fig. 3. Combinatorial synergy between AZT and antibiotics is dependent on thymidine kinase activity. (a) Checkerboard broth microdilution assays between AZT and the indicated antibiotics for wild-type ST313 grown in LPM. Darker shades of red indicate higher bacterial cell density; white indicates the absence of bacterial growth. (b) Compound treatment (AZT, 128 μg mL⁻¹; ciprofloxacin, 2 μg mL⁻¹; colistin, 128 μg mL⁻¹; individually or in combination) and bacterial infection of RAW264.7 macrophages for 6 h. Bars indicate mean and s.e.m. Groups were compared against control-treated macrophages (equivalent concentration of DMSO) via one-way ANOVA and corrected for multiple comparisons with Sidak's test. (c) As in panel b, for 20 h of bacterial infection. (d) Potency of AZT against wild-type, , and Δtdk ST313 iNTS grown in LPM. Growth is normalized to a DMSO control (set to 100%), dots and error indicate mean and s.e.m. for three biological replicates. (e) and (f) Loss of combinatorial synergy in tdk mutants. Checkerboard broth microdilution assays between AZT and the indicated antibiotics for Δtdk ST313 (e) and ST313 (f) grown in LPM. Darker shades of red indicate higher bacterial cell density; white indicates the absence of bacterial growth.