Heparinase Is Essential for Pseudomonas aeruginosa Virulence during Thermal Injury and Infection.

The opportunistic pathogen is a major cause of sepsis in severely burned patients. If it is not eradicated from the wound, it translocates to the bloodstream, causing sepsis, multiorgan failure, and death. We recently described the heparinase-encoding gene, , whose expression was significantly enhanced when strain UCBPP_PA14 (PA14) was grown in whole blood from severely burned patients. Further analysis demonstrated that contributed to the virulence of PA14 in the model. In this study, we utilized the murine model of thermal injury to examine the contribution of to the pathogenesis of during burn wound infection. Mutation of reduced the rate of mortality from 100% for mice infected with PA14 to 7% for mice infected with PA14:: While comparable numbers of PA14 and PA14:: bacteria were recovered from infected skin, only PA14 was recovered from the livers and spleens of infected mice. Despite its inability to spread systemically, PA14:: formed perivascular cuffs around the blood vessels within the skin of the thermally injured/infected mice. Intraperitoneal inoculation of the thermally injured mice, bypassing the need for translocation, produced similar results. The rate of mortality for mice infected with PA14:: was 0%, whereas it was 66% for mice infected with PA14. As before, only PA14 was recovered from the livers and spleens of infected mice. These results suggest that plays a crucial role in the pathogenesis of PA14 during burn wound infection, most likely by contributing to PA14 survival in the bloodstream of the thermally injured mouse during sepsis.