Fig. 4

CBS suppresses the evolution of NDM-1 and boosts the antimicrobial activity of MER for the treatment of NDM-1-positive bacterial infection. a, b Heat plot visualizing the mutation frequency of (a) NDM-HK and (b) NDM-HK PCV exposed to MER in the presence of increasing concentrations of CBS. c Bar chart showing MPC values of MER in the presence of increasing concentration of CBS against NDM-HK and NDM-HK PCV. d Resistance acquisition curves during serial passage with the subinhibitory concentration of MER or combination of MER and CBS against NDM-HK. MIC test was performed every four passages. The inset shows the normalized expression level (by Western blot) of NDM-1 in the WT NDM-HK, 20^th passage of NDM-HK selected by MER or by combination of MER and CBS. Original western blots is shown in Supplementary Figure 10. e Bar chart showing associated-bacterial load in the in vitro infection model. The concentrations (μg mL⁻¹) used are 8, 16, and 32 μg mL⁻¹ for MER and 32 μg mL⁻¹ for CBS. f Survival curves showing efficacies in a murine peritonitis infection model with the use of mucin. BALB/c mice were infected by a lethal dose of NDM-HK via intraperitoneal injection. Four groups of mice were treated with vehicle control, monotherapy of MER (5 mg kg⁻¹), CBS (20 mg kg⁻¹), or combination therapy of MER and CBS. P < 0.001, Mantel–Cox test, significant difference from the vehicle control. Eight mice per group were used in vehicle control, monotherapy of MER, or CBS and 12 mice per group in the combination therapy