FIG. 6.
F. tularensis ΔpyrF mutants retain virulence in animal models of infection. Chicken embryos (A) or mice (B) were infected with the indicated strains. Data represent a combination of 3 (A) or 2 (B) experiments and are shown as Kaplan-Meier survival curves depicting percent survival over time. (A) Chicken embryos were infected with ∼103, ∼105, or ∼107 CFU. All bacterial strains were used to infect chicken embryos in three experiments except LVS ΔdeoB, which was used in only one trial. Twenty embryos were used for LVS ΔpyrF, 16 for LVS ΔpyrF/pF8pyrFfull2 (comp), 16 for LVS ΔpyrF/pFNLTP8 (vector), and 6 for LVS ΔdeoB. For each experiment, the actual numbers of CFU administered to the chicken embryos were as follows: for LVS, 8.0 × 102, 2.8 × 105, and 5.0 × 107; for LVS ΔpyrF, 1.6 × 103, 9.0 × 104, and 1.2 × 107; for LVS ΔpyrF/comp, 1.1 × 103, 1.8 × 105, and 4.6 × 107; for ΔpyrF/vector, 6.2 × 102, 2.6 × 105, and 1.7 × 107; and for LVS ΔdeoB, 2.5 × 102. P was <0.0001 for LVS versus LVS ΔdeoB. (B) Mice were infected (i.t.) with ∼101 or ∼103 CFU of each strain. Ten mice (two experiments) were used for each infecting strain except LVS, for which five mice (included in only one experiment) were used. For each experiment, the actual numbers of CFU administered to mice were as follows: for Schu S4, 37 and 350; for Schu S4 ΔpyrF, 14 and 500; for Schu S4 ΔpyrF/comp, 19 and 250; for Schu S4 ΔpyrF/vector, 49 and 850; and for LVS, 850. A subset of mice was sacrificed at 2 h postinfection, and their lungs were homogenized and plated to confirm the efficacy of bacterial delivery to pulmonary tissue, which indicated comparable rates of delivery for all strains (not shown). P was 0.0002 for LVS versus Schu S4 ΔpyrF; P was <0.0001 for Schu S4 versus Schu S4 ΔpyrF.