Fig. 2: Amplification generates a subpopulation continuum responsive to inhibition.
a PAP of RS plated on cefiderocol, with the proportion of surviving colonies in the black line on the left y-axis, with mean and standard deviation shown. blaSHV-5 abundance was quantified from the samples collected at each concentration by qPCR and log10 transformed. Each dot indicates a biological replicate, with median and quartiles indicated graphed on the right y-axis, from two independent experiments; total n = 6 for PAP and n = 7 for qPCR, one-way mixed-effects ANOVA analysis with Geisser-Greenhouse correction and Dunnett’s multiple comparison test, F (2.387, 13.85) = 112.1. b Details of the populations collected on 8 µg/mL or 32 µg/mL cefiderocol are shown. c A model of the RS population: as the concentration of cefiderocol increases, the proportion of the surviving cells decreases. The cefiderocol resistance of the surviving resistant cells increases with an increase in the blaSHV-5 abundance. d PAP of strain RS or the isogenic ΔblaSHV-5 mutant plated on cefiderocol or cefiderocol and 4 µg/mL clavulanate. The mean and standard deviation are shown from two independent experiments with 3 biological replicates each. e Strain RS was plated on MHA containing cefiderocol and clavulanate as indicated. The proportion of the surviving population is the line graph with the left y-axis, with means and standard deviation. The corresponding log10 transformed gene abundance is graphed on the right y-axis, where each point indicates a biological replicate from two independent experiments with n = 9 total biological replicates, one-way mixed-effects ANOVA, F (2.742, 21.15) = 181.8 with Geisser-Greenhouse correction and Dunnett’s multiple comparison test. Source data are provided as a Source Data file.
