Figure 8

CA439 is effective against highly resistant colistin strains. Checkerboard assay showing CA439-colistin combination in (a) a mgrB mutant or (b) in a wild type strain overexpressing mcr-1. Dark blue regions represent higher cell density. Data represent the mean OD (600 nm) of at least three biological replicates. Right panel shows the CFU counting obtained in each growth condition: DMSO (LB-medium with the addition of DMSO), CA439 (25 μM CA439 alone), colistin (1.25 μg mL⁻¹ and 2.5 μg mL⁻¹ colistin alone for ΔmgrB and mcr-1 respectively) and CA439 + colistin (25 μM CA439 + 1.25 μg mL ⁻¹ colistin for ΔmgrB or 2.5 μg mL⁻¹ colistin for mcr-1). Fractional inhibitory concentration (FIC) was obtained by dividing the colistin MIC in the presence of CA439 (1.25 μg mL⁻¹ for ΔmgrB and 2.5 μg mL⁻¹ for mcr-1) by the colistin MIC in the absence of CA439 (20 μg mL^-1 for both strains). Statistical analysis was performed using one-way ANOVA with Tukey’s correction multiple comparison test (****P < 0.0001; ***P < 0.001; **P < 0.01; ns, no significant differences).