Fig. 5.

SIP-mediated regulation of virulence genes is critical for GAS pathogenesis in mouse models of infection. (A) Twenty outbred CD-1 mice were inoculated i.p. with each indicated strain. Kaplan–Meier survival curves with P values derived by the log-rank test are shown. p.i., postinfection. (B) Twenty outbred CD-1 mice per strain were injected i.m. with each indicated strain. Kaplan–Meier survival curves with P values derived by the log rank-test are shown. (C) Gross (Top) and microscopic (Bottom) analyses of hind-limb lesions from mice infected with each indicated strain. (Top) Larger lesions with extensive tissue damage in SpeB-expressing strains are boxed (white boxes). (Bottom) Areas of disseminated lesions in the infected tissues are boxed (black box), whereas confined, less destructive lesions are circled. (D) Fifteen immunocompetent hairless mice were infected s.c. with each indicated strain, and the lesion area produced by each strain was determined. The lesion area was measured and graphed (mean ± SEM). The P value was derived by two-way ANOVA. (E) Histopathologic analysis of lesions from mice infected s.c. with each indicated strain. Areas of disseminated lesions and ulcerations on the skin surfaces caused by SpeB-producing strains are marked by arrows, whereas confined, less destructive lesions caused by SpeB-deficient strains are boxed. [Scale bars: C and E, 2.2 mm × 1.7 mm (y axis × x axis) at 4× magnification.]