Fig. 3: FAST platform generates PNAs that can potentiate activity of traditional small molecule antibiotics.

a Using the STRING database of protein network interactions (data shown in Supplementary Figure S10), we found a positive correlation, Pearson’s r = 0.908 and p < 0.001, between growth inhibition of PNA homologous with target bacteria and average node degree, the number of interactions of protein has in the average network. b–m Subsequent growth curves and bar plots show bacteria without treatment, or treatment with PNA alone (10 µM), or antibiotic alone, or PNA and antibiotic combined. Antibiotic concentrations were (from top to bottom) 2 µg/mL tetracycline (TET), 4 µg/mL gentamicin (GEN), and 8 µg/mL chloramphenicol (CHL). b, f, j The first column shows representative growth curves over 24 h of each treatment. Panels b–e and f–i show treatment of CRE E. coli with PNAs targeting essential and non-essential genes respectively. Panels j–m show treatment of ESBL KPN with PNAs targeting essential genes. All bar plots are the average OD (600 nm) of each treatment at 24 h normalized to no treatment at 24 h. S values above the bar plots were obtained using the Bliss Independence model and indicate synergistic interaction between PNA and antibiotic at 24 h, an asterix indicates significance at α = 0.05. Grey circles indicate individual biological replicates. Panels n–p show select heat maps of synergy values at 24 h of checkerboard combination assays (Figures S12-13). q Plotting the S values representing synergy against the target protein’s average node degree shows a negative correlation (Pearson’s r  = −0.3017, p = 0.0314). All data shown are the average of at least three biological replicates with standard deviation shown as error bars.