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. 2020 Aug 29;10(23):10697–10711. doi: 10.7150/thno.45951

Figure 7.

Figure 7

Melatonin rescues colistin activity in three animal infection models. (A) Scheme of the experimental protocols for three animal infection models. In three infection models, animals were infected by colistin-resistant E. coli B2 (mcr-1), and treated with a single dose of colistin, melatonin or their combination at one-hour post-infection. In the Galleria mellonella infection model (1), survival rate of larvae (n = 10 per group) was monitored during 5 days, related to Figure 7B. In the mouse peritonitis-sepsis infection model (2), the percentage of surviving mice (n = 8 or 9 per group) was recorded during 7 days, related to Figure 7C. In neutropenic mouse thigh infection model (3), thigh muscle bacterial loads in single and combination therapy (n = 8 per group) were counted at 2 days post-infection, related to Figure 7D. (B) Combination of colistin (10 mg/kg) and melatonin (50 mg/kg) significantly improved survival rate of G. mellonella larvae (n = 10 per group) infected by colistin-resistant E. coli (mcr-1) compared with colistin monotherapy (10 mg/kg). P values were determined by log-rank (Mantel-Cox) test. (C) Combination of colistin and melatonin profoundly increased survival rate of mice infected by colistin-resistant E. coli (mcr-1) during 7 days post-infection in a dose-dependent manner. BALB/c mice (n = 8 or 9 per group) were given a lethal dose of E. coli (3.0 × 108 CFUs), and treated with a single dose of colistin (10 mg/kg), melatonin (50 mg/kg), a combination of colistin plus melatonin (5 + 50 mg/kg, 10 + 20 mg/kg and 10 + 50 mg/kg), or PBS by intraperitoneal injection. P values were determined by log-rank (Mantel-Cox) test. (D) Decreased bacterial load in the neutropenic mouse thigh infection model by combination therapy. Neutropenic BALB/c mice (n = 8 per group) were intramuscularly given a non-lethal dose of E. coli (1.0 × 105 CFUs), and treated with a single dose of colistin (10 mg/kg), melatonin (50 mg/kg), a combination of colistin plus melatonin (5 + 50 mg/kg, 10 + 20 mg/kg and 10 + 50 mg/kg), or PBS by intraperitoneal injection. P values were determined by Mann-Whitney U test. Data are presented as mean ± SD.