Fig. 6: In vivo analysis of the efficacy of RFB14KH against Mycobacterium tuberculosis infection. | Nature Communications

Fig. 6: In vivo analysis of the efficacy of RFB14KH against Mycobacterium tuberculosis infection.

From: A long-acting formulation of rifabutin is effective for prevention and treatment of Mycobacterium tuberculosis

Fig. 6

a Experimental schema for pre-exposure treatment efficacy testing of LA-RFB. BALB/c mice were untreated (n = 4) or treated with a single subcutaneous injection of placebo (n = 6) or RFB14KH (n = 6) formulations. Two weeks after treatment, mice were exposed to Mtb. Control untreated mice were used to determine the dose of exposure 24 h after infection (n = 4). ISFI treated mice were analyzed for Mtb infection 4 weeks post-exposure. b Bacterial burden in lung, liver, and spleen of placebo (n = 6) and RFB14KH (n = 6) treated mice 4 weeks after Mtb exposure, mean +/−SEM are shown (#P = 0.0022 Mann–Whitney U test). c H&E staining of lung sections shows pathological changes in mice treated with placebo but not in mice treated with RFB14KH. Representative sections from 6 placebo and 6 RFB14KH treated mice are shown d Experimental schema for post-exposure LA-RFB treatment. BALB/c mice (n = 22) were exposed to Mtb; 24 h later, a group of 4 was analyzed to determine the exposure dose. Mtb infection was assessed again 1-week post exposure in a group of 6 mice to determine the levels of infection. At this time the remaining infected mice were treated with placebo (n = 6) or RFB14KH (n = 6). Animals were harvested and analyzed for Mtb infection 3 weeks later (4 weeks post exposure to Mtb). e Bacterial burden in mice 7 days post Mtb exposure (n = 6). f Bacterial burden 4 weeks post Mtb exposure, mean +/− SEM are shown (n = 6 per group, &P = 0.0022, Mann–Whitney U test). g H&E staining of lung sections show pathological changes in mice treated with placebo but not in mice treated with RFB14KH. Representative sections from 6 placebo and 6 RFB14KH treated mice are shown. Scale bars in H&E images in c and g are 300 μm in low magnification images and 50 μm in higher magnification images. Dotted lines in panels b, e, and f indicate the limit of detection. Arrows in panels c and g indicate lesions caused by Mtb. Source data for panels b, e, and f are provided as a Source data file and in Supplementary Tables 2, 3, and 4.

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