Figure 1. Active IsdB immunization renders mice susceptible to sepsis following SSI.

(A) Anti-IsdB titers in sera of actively immunized and adjuvant control mice were determined by ELISA before transtibial implant surgery (n = 10 per group, ***P < 0.0001 via Mann-Whitney test, lower limit of detection <100). (B) Longitudinal BLI images, with heatmap signal intensities, of a representative IsdB actively immunized mouse, with evidence of MRSA dissemination from the surgical site region of interest (ROI, red circled region) to internal organs (red arrow). (C) BLI signal within the tibial ROI are shown for individual mice, with the mean for the group (*P < 0.05 on day 7 via exact Wilcoxon test with an adaptive Hochberg multiplicity adjustment). (D) The body weight of the mice actively immunized against IsdB protein, or adjuvant only control, was obtained on the indicated days before and after challenge. Note that IsdB-immunized mice did not gain weight after MRSA challenge (n = 10 per group, *P < 0.05 on day 14 via 2-way ANOVA). Images of liver abscess (E) and pale kidneys (F) in anti-IsdB mAb–treated mice. (G) CFUs on the tibial pin and in internal organs were determine on day 14 after infection. The incidence and mean level of CFUs on the implants in both groups were similar (lower limit of detection <50). CFUs in internal organs of control mice were not detected (N.D.), while IsdB-immunized mice display evidence of MRSA dissemination (n = 10 per group, *P < 0.05 via Fisher’s exact test, lower limit of detection <10).