Fig. 5: Translation bottlenecks can predict antibiotic interactions.
From: Mechanisms of drug interactions between translation-inhibiting antibiotics
a Example of drug-interaction prediction based on the equivalent translation bottlenecks. The drug interaction between CHL and an antibiotic that targets initiation can be predicted through mimicking the initiation inhibition by limiting the expression of initiation factor (infB). b The response surface of CHL combined with the inducer for the initiation (infB) bottleneck shows mild alleviation. This response surface contains information about the interaction between CHL and any antibiotic that interferes with initiation. The inducer axis is remapped into mimicked antibiotic concentration (Fig. 4c, d). c Left: resultant prediction of the response surface for the initiation-inhibiting antibiotic KSG and CHL. Right: measured KSG-CHL response surface for direct comparison; strong antagonism is observed as predicted. d A point-by-point comparison of predicted and measured response surfaces (Pearson’s ρ = 0.98). e Schematic showing antibiotics and their equivalent translation factor bottlenecks. Drug interactions with these antibiotics can be predicted for any antibiotic with a known response to the equivalent bottleneck. Color-code shows cluster identity from Fig. 3e. f Comparison of predicted and measured response surfaces for different antibiotics in combination with antibiotics that have a factor analog. Top row: scatter plots as in (d); bottom row: predicted and measured response surfaces, respectively. Remapping correctly predicts antagonism (KSG-LCY), suppression (FUS-CHL), strong antagonism (KSG-STR), and additivity (TET-CHL).
