Extended Data Fig. 3: In vitro and in vivo bactericidal activity of zosurabalpin against MDR resistant A. baumannii isolates.
From: A novel antibiotic class targeting the lipopolysaccharide transporter
a, An exponential culture of ACC01073 was challenged with sub MIC, MIC (2 mg/L in CAMHB with 20% HS) and multiple MIC of zosurabalpin (ZAB) or colistin (CST) at 4x MIC. Kinetic of killing determined by sampling, plating and CFU counting at different time points over 24 h. Data from one representative replicate of 3 independent experiments displayed. b, c, In vivo efficacy of zosurabalpin in mouse model of infections induced by MDR A. baumannii. b, Sepsis induced by intraperitoneal bacterial inoculation of ACC00445 (zosurabalpin MIC = 0.25 mg/L in CAMHB with 20% HS) in immunocompetent mice. Treatment administered subcutaneously (s.c.) at 1 and 5 h post-infection. Kaplan-Meier survival curve shows percentage of mice survival for each group treated with vehicle, Meropenem (MEM, 80 mg/kg) or varying doses of zosurabalpin (n = 10/group) over 7 days. c, Thigh infection induced by bacterial intramuscular inoculation of ACC01085 (zosurabalpin MIC = 0.5 mg/L in CAMHB with 20% HS) in immunocompromised mice. Treatment, starting 2 h post-infection (0 h), administered s.c. (n = 4 mice/ treatment group or vehicle) each 6 h over 24 h for zosurabalpin and each 8 h for colistin. Dose response curve of zosurabalpin total daily doses (mg/kg/day) measured as bacterial burden reduction (colony forming units, CFU) in infected thigh (8 thighs, 8 read outs for bacterial counts). Data are expressed as scatterplot distribution. The centre bars represent the mean ± SD (error bars). Statistical significance of the difference in bacterial count between control and treated mice was calculated by using the one-factor ANOVA followed by Dunnett’s Multiple Comparison Test (p < 0.05 significant), **p < 0.01, ***p < 0.001 and ****p < 0.0001 vs T0h. The ‘skull and crossbones’ symbol indicates mortality prior to 24 h endpoint (n = 1).