FIGURE 7.

Peptide activity in human blood infected by bacteria and in an animal model of P. aeruginosa sepsis. The indicated Gram-negative and Gram-positive bacterial strains (2 × 10⁸ cfu/ml) were added to 50% citrate blood (diluted in PBS), followed by addition of peptide at 60 μm. A, antibacterial effects (after 1 h) of the indicated peptides were determined. The number of bacteria was analyzed (y axis). B, using the same material, hemolysis in human blood in presence of the indicated bacteria as well as peptides was analyzed. Hemolysis was assessed after 1 h. 1% Triton X-100 was used as positive control (yielding 100% permeabilization). C, effects of FFF21 in mice infected by P. aeruginosa 15159. FFF21 suppresses bacterial dissemination to the spleen, liver and kidney. C57BL6 mice were injected intraperitoneal with P. aeruginosa bacteria, followed by intraperitoneal injection of 0.5 mg of FFF21 or buffer only, and the cfu of P. aeruginosa in spleen, liver, and kidney was determined after a time period of 12 h (n = 8 for controls and treated, p < 0.05 for spleen, liver, and kidney. Horizontal line indicates median value). D, platelet counts were analyzed in blood from the same experiments. E, in a separate experiment, mice were challenged with 2 × 10⁷ cfu/ml P. aeruginosa Xen41 (intraperitoneal) and FFF21 (0.5 mg) was administered intraperitoneal 30 min and 2 after injection of bacteria (n = 5 in each group). F, bioluminescence signal of whole individual mice was measured using the regions of interest (ROI) total count analysis at 0 and 10 h after bacterial injection. G, mice were imaged immediately after bacterial challenge and 10 h after post-infection.