Figure 5

Drug combinations involving disulfiram. Disulfiram along with kanamycin, clozapine, amoxicillin and chlorpromazine are all predicted to be individually effective antileishmanial agents because they all act on both genes in a synthetic lethal pair. However, they also have the potential to act synergistically to produce growth inhibition in L. major. Therefore, for predictions of model-guided superadditivity, it is assumed that the interactive relationship present between genes in a synthetic lethal deletion would translate directly to any associated drug combinations. In panels A, B, C and D, the results of one concentration profile of disulfiram + kanamycin, disulfiram + clozapine, disulfiram + amoxicillin and disulfiram + chlorpromazine as evaluated against L. major promastigotes are presented, respectively. The theoretical additivity bar was computed using the bliss additivity metric upon comparing the effects of the individual drugs. A two-sample t-test comparing two means was used to determine statistical significance between the theoretical and experimental combinations. Concentrations are provided in parentheses. Error bars signify standard error. The y-axis indicates fractional experimental effect of inhibition or growth relative to "No Drug" control (0 equals no inhibition, 1 equals max inhibition). All data were generated at 48 hours post addition of alamarBlue dye.