Bactericidal effect of BPaL and BPaS in TB mouse models after 4-weeks of treatment BALB/c and C3HeB/FeJ female mice were chronically infected with a low dose aerosol infection of Mtb Erdman strain to deliver ∼75 and ∼100 bacilli respectively. Post-infection, BALB/c and C3HeB/FeJ mice were rested for 4 and 8-9 weeks respectively until they were randomly assigned to the study groups. The mice were treated with monotherapy of linezolid or spectinamide 1599 or combination therapy of BPaL, BPa or BPaS for 4 weeks. Bedaquiline (B), pretomanid (Pa) and linezolid (L) were administered at 25, 100 and 100 mg/kg respectively by oral gavage for 5/7 a week while spectinamide 1599 at 50 and 100 mg/kg in BALB/c and C3HeB/FeJ TB models respectively for 3/7 a week on the alternate days via intrapulmonary aerosol delivery. On the third day of the last treatment, the mice were euthanized, and their lungs and spleen were collected. The organs were homogenized, serially diluted and plated on 7H11 agar with 4% charcoal (to avoid drug carry-over effect) to determine bacterial burden in the form of colony forming units (CFU) in each sample. CFU were enumerated after 4-6 weeks of incubation at 37 °C and expressed as log10.C3HeB/FeJ and BALB/c TB models showing efficacy of monotherapy (A-D) and combination therapy (E-H). The C3HeB/FeJ graphs (E&G) represent the pooled data from three independent studies (n=3-8 each, Figures S1-3) and two of the three studies contained BPa as a reference control. The BALB/c graphs (F&H) represent the pooled data from two independent studies (n=5 each, Figures S8-9). Statistical significance was calculated using one-way ANOVA with Tukey’s multiple comparison test, p < 0.05 was considered significant and ** = p<0.001, *** = p<0.0001, **** = P<0.0001. UnRx = untreated, L = linezolid, S = spectinamide 1599, LOD: limit of detection.