S-MGB-364 and S-MGB-364-NIV treatment is non-toxic and reduced the mycobacterial lung burden in HN878 Mtb-infected mice. (a) C57BL/6 mice (n = 6 per group) were infected with Mtb HN878 via intranasal challenge. At 1, 2, 3 and 4 weeks post-infection, mice were intranasally treated with 10 mg/kg of S-MGB-364, S-MGB-364-NIV, or saline. Mice were sacrificed at 5 weeks post-infection and lungs were isolated and homogenized for cfu enumeration. Bacterial load (cfu) measured in lungs of mice infected with an infective dose of (b) 1000 cfu and (c) 100 cfu Mtb HN878 and intranasally treated with S-MGB-364, S-MGB-364-NIV, or saline. (d and e) Supernatants from lung homogenates of mice that were infected with 100 cfu Mtb HN878 were collected for analysis of cytokine/chemokine concentrations by ELISA. (f) Liver aspartate transaminase (AST), and alanine transaminase (ALT) levels were measured in the sera of Mtb-infected (100 cfu) mice treated intranasally with S-MGB-364, S-MGB-364-NIV, or saline. Data are shown as mean ± SEM. Students t-test or one-way ANOVA: *P < 0.05, **P < 0.01, and ***P < 0.001.