Figure 6

Difference surfaces measure the departure of measured response from that expected from Loewe additivity for (a, c, e) planktonic bacteria and (b, d) biofilms. (f) For 4219D biofilms, we measure the departure from a strictly additive surface. By our construction, a negative value for % difference indicates a synergistic interaction between tobramycin and bicarbonate at the corresponding combination, and a positive height indicates an antagonistic interaction. (a) The difference surface for planktonic PAO1 is consistently negative within the 0% difference border, indicating that the interaction between tobramycin and bicarbonate is everywhere synergistic. This surface is rendered semi-transparent for better visualisation. (b) The difference surface for biofilm PAO1 is positive at most locations, indicating overall antagonism, and negative at a few locations, indicating that within that limited parameter space the tobramycin-bicarbonate interaction is synergistic against the biofilm. (c) The difference surface for planktonic 3470C bacteria ranges between −50 and +50%, and the integral of this surface over the region shown is close to zero. This indicates that the net synergy between tobramycin and bicarbonate is negligible when averaged over the combinations measured. (d) The difference surface for biofilm 3470C is positive at most locations, indicating overall antagonism, and negative at a few locations, indicating that within that limited parameter space the tobramycin-bicarbonate interaction is synergistic against the biofilm. (e) The difference surface for planktonic 4219D bacteria ranges between −50 and +50%, and the integral of this surface over the region shown is −3.9, indicating overall net synergy between tobramycin and bicarbonate. (f) For the biofilm, the difference surface for biofilm 4219D is positive at most locations and the integral over the area shown is +67, indicating that the combination of tobramycin and bicarbonate against this biofilm has the strongest overall antagonism of all the systems we measure.