Fig. 3. PZA reverses TB-induced PARP1 activation in mouse lungs.

a Schematic study overview. Female C3HeB/FeJ mice were aerosol infected with M.tb H37Rv (implantation: 111 ± 9 CFU) and administered PZA (150 mg/kg), the PARP inhibitor talazoparib (Tp; 0.5 mg/kg) or vehicle (1.97% DMSO in 0.5% CMC), alone or in combination with the TB antibiotic RIF (10 mg/kg), 5 days/week for 2 months starting 1 month post infection. Bacterial burden and PAR levels were assessed before and after treatment and in age-matched uninfected control mice. b Representative Western blots showing PAR levels (top) or the loading control β-Actin (bottom) in mouse lungs after 2 months of treatment. Each lane represents an individual mouse. c Densitometric analysis showing the change in ß-Actin-normalized lung PAR intensity relative to the mean in vehicle-treated mice. n = 6 (uninfected) or 8 (all other groups). Each symbol represents an individual mouse and bars the group mean ± SEM. ns not significant (RIF vs. vehicle); *p = 0.0159 (PZA vs. vehicle) or 0.0433 (uninfected vs. vehicle); **p = 0.0071 (Tp vs. vehicle) by two-way ANOVA with uncorrected Fisher’s least significant difference (LSD) test. d Corresponding difference in lung bacterial burden following treatments compared to vehicle-treated mice. n = 9 (vehicle) or 8 (all other groups). Each symbol represents an individual mouse and bars the group mean ± SEM. ns not significant (Tp vs. vehicle); *p = 0.0425 (PZA vs. vehicle); **p = 0.0013 (PZA vs. RIF); ****p < 0.0001 (RIF vs. vehicle) by one-way ANOVA with Tukey’s multiple comparisons test. Mice treated with PZA or Tp had significantly reduced lung PAR levels comparable with uninfected mice. PAR levels in RIF-treated mice were not statistically different from vehicle-treated mice, even though the bacterial burden was significantly more reduced by RIF than by PZA or Tp. Source data are provided as a Source Data file.