Journal: Cell

Article Title: Discovery of natural-product-derived sequanamycins as potent oral anti-tuberculosis agents

doi: 10.1016/j.cell.2023.01.043

Figure Lengend Snippet: In vivo activity of SEQ-9 in the lungs of Mtb-infected BALB/c mice after treatment with SEQ-9 Histograms represent the mean lung log 10 CFU counts (5–10 mice per group). Error bars in all panels represent SEM. The number following the compound abbreviation indicates the dose in mg/kg/day (unless otherwise indicated, ∗ p < 0.05, ∗∗ p < 0.01, and ∗∗∗ p < 0.001, compared with no treatment (one-way ANOVA). (A) SEQ-9 dose-ranging in an acute TB mouse model. CFU counts after 4 weeks of treatment. Day 3 indicates lung CFU counts at treatment initiation (3 days after infection). (B) SEQ-9 dose-ranging in the mouse model of chronic TB: CFU counts after 4 weeks of treatment. Day 3 indicates lung CFU 3 days after infection. Day 31 indicates lung CFU counts at treatment initiation (28 days after infection). A PEG200/Tween80/citrate buffer (PEG-Tw) 100 mM (70/5/27) pH 4 formulation was used for SEQ-9, whereas MCT was used for rifampicin (RIF) and linezolid (LIN) ( ∗ p < 0.05 and ∗∗ p < 0.01, compared with no treatment. Kruskal-Walllis test). (C) SEQ-9 dose-ranging in short (highly) acute mouse model of TB. Day 1 indicates lung CFU counts at treatment initiation (1 day after infection). SEQ-9 (Lip/2) and control (day 11 Lip/2) groups are from an independent study using a lipidic formulation described in Figure S8 and Table S7 and were compared by Student’s t test: ###p < 0.001.

Article Snippet: A mid log phase Mtb H37Rv culture was incubated overnight in Middlebrook 7H9 broth (supplemented with + 10 % OADC + 0.05% Tween80 + 0.4% glycérol) with subinhibitory concentrations of clarithromycin or SEQ-9 (0.125μg/ml and 0.25μg/ml).

Techniques: In Vivo, Activity Assay, Infection

Journal: Cell

Article Title: Discovery of natural-product-derived sequanamycins as potent oral anti-tuberculosis agents

doi: 10.1016/j.cell.2023.01.043

Figure Lengend Snippet: SEQ-9 kill kinetics of Mtb H37Rv in 7H9 broth culture, related to Figure 5 Bacterial cultures with various SEQ-9 concentrations or 1% DMSO were followed during 11 days. For each time, CFU count was assessed by plating on 7H11 agar plates. The number following the compound abbreviation indicates the concentration in μM.

Article Snippet: A mid log phase Mtb H37Rv culture was incubated overnight in Middlebrook 7H9 broth (supplemented with + 10 % OADC + 0.05% Tween80 + 0.4% glycérol) with subinhibitory concentrations of clarithromycin or SEQ-9 (0.125μg/ml and 0.25μg/ml).

Techniques: Concentration Assay

Journal: Cell

Article Title: Discovery of natural-product-derived sequanamycins as potent oral anti-tuberculosis agents

doi: 10.1016/j.cell.2023.01.043

Figure Lengend Snippet:

Article Snippet: A mid log phase Mtb H37Rv culture was incubated overnight in Middlebrook 7H9 broth (supplemented with + 10 % OADC + 0.05% Tween80 + 0.4% glycérol) with subinhibitory concentrations of clarithromycin or SEQ-9 (0.125μg/ml and 0.25μg/ml).

Techniques: Mutagenesis, Recombinant, Cell Culture, Methylation, Amplification, Software, Microscopy, RNA Extraction, Real-time Polymerase Chain Reaction