Fig 5.
Survival and protection of mice infected with wild-type K96243 and its isogenic ΔrelA ΔspoT mutant. (A and B) C57BL/6 mice were challenged intranasally with an intended dose of 2,500 CFU (acute challenge [A]) or 500 CFU (chronic challenge [B]). Actual infection doses for each experiment are given in parentheses. Log rank tests confirmed a significant difference in survival between the wild type and the ΔrelA ΔspoT mutant in both cases (P < 0.001 and P < 0.05, respectively). (C to E) C57BL/6 mice were immunized intranasally with 1 × 105 CFU of strain 2D2 or K96243 ΔrelA ΔspoT. After 5 weeks of incubation, mice were challenged intranasally with 1,000 CFU of B. pseudomallei strain 576. Mice were monitored for survival, and numbers are plotted as Kaplan-Meier survival curves (C). Log rank tests confirmed a significant difference in survival of the K96243 ΔrelA ΔspoT and the 2D2 cohorts compared to the saline control (P < 0.01 and P < 0.05, respectively). At day 55 after infection with the wild type, bacterial burdens were assessed in lungs (D) and spleens (E) of survivors. Note that only one mouse had survived up to this time point in the saline-treated sample group. The spleen of this mouse and that of one survivor in the K96243 ΔrelA ΔspoT sample group had extremely large abscesses and could not be harvested. N.A., not available.