When the Most Potent Combination of Antibiotics Selects for the Greatest Bacterial Load: The Smile-Frown Transition
(a) The strain E. coli K12 (AG100) undergoes the smile-frown transition within two days (the value of α from the α-test is shown in the left figure and quoted ± s.e.; day-1 α-test at 18 h: α>0, df = 27, t = 14.84, p<10−13 with θopt(18 h) = 0.04±0.01; day-2 α-test at 18 h: α<0, df = 27, t = −7.45, p<10−7). The right-hand plot shows a dynamic of the value of −α from the α-test through time with antagonism following synergy where the plot passes through zero, just as in Figure 4 for the strain MC4100. (b) E. coli K12 AG100A(Δacr) does not exhibit the smile-frown transition by day 3 and the drug interaction is still synergistic then (α-test at 24 h on day 3: α>0, df = 27, t≈3.95, p<0.00052; see Section 7.2 in Text S1). The right-hand figure shows that the plot of −α from the α-test does not pass through zero at any time, the drug interaction is therefore stable and synergistic over the entire period of observation.