Fig. 4. rel_Mtb deficiency is associated with attenuated Mtb phenotypes in vivo.

(A) The stringent response is required for Mtb tolerance to INH during the chronic phase of infection in mouse lungs. BALB/c mice were aerosol-infected with WT Mtb H37Rv or Δrel, and daily (5 days/week) treatment with INH (10 mg/kg) by esophageal gavage was initiated 28 days after infection. ****P < 0.0001. The growth phenotype and treatment response of rel Comp was similar to that of the WT strain (see Results). (B) Rel_Mtb is required for Mtb-induced mortality of immune-competent mice with human-like TB pathology. Survival of C3HeB/FeJ mice following a low-dose aerosol infection with either WT or rel_Mtb-deficient (Δrel) strains of Mtb was monitored for 40 weeks after infection. The starting number of mice in each group was 15. Mouse survival is significantly improved following infection with Δrel relative to WT (P < 0.0001).