Fig. 3.

Drug combination screening identifies synergistic/antagonistic combinations with antimycobacterial antibiotics. (A) Individual κ values and confidence intervals were calculated using the BRAID response surface model and plotted. κ > 0 are considered synergistic and κ < 0 are considered antagonistic with values further from 0 representing stronger interaction profiles (increase for synergy, decrease for antagonism) for that combination. Error bars crossing κ = 0 indicate a nonstatistically significant interaction. (B–G) Heatmap of individual checkerboard assay results where percent viability was determined by resazurin conversion over the final 24 h of a 72-h incubation at 37 °C and normalized to no drug (100% viability) and cell death controls (CLR 6 µg/mL; 0% viability) with darker blue indicating higher reduction potential (surrogate for cell viability). Checkerboard plates of 2593 in combinations with (B) AMK, (C) CLR, (D) LZD, (E) CEFOX, (F) BDQ, and (G) CLO. Median % viability values from three independent replicates were plotted. Abbreviations: AMK, amikacin; BDQ, bedaquiline; CEFOX, cefoxitin; CLO, clofazimine; CLR, clarithromycin; LZD, linezolid.