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

ABSTRACTThe opportunistic pathogenPseudomonas aeruginosais 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 theP. aeruginosaheparinase-encoding gene,hepP, whose expression was significantly enhanced whenP. aeruginosastrain UCBPP_PA14 (PA14) was grown in whole blood from severely burned patients. Further analysis demonstrated thathepPcontributed to thein vivovirulence of PA14 in theCaenorhabditis elegansmodel. In this study, we utilized the murine model of thermal injury to examine the contribution ofhepPto the pathogenesis ofP. aeruginosaduring burn wound infection. Mutation ofhepPreduced the rate of mortality from 100% for mice infected with PA14 to 7% for mice infected with PA14::hepP. While comparable numbers of PA14 and PA14::hepPbacteria were recovered from infected skin, only PA14 was recovered from the livers and spleens of infected mice. Despite its inability to spread systemically, PA14::hepPformed 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::hepPwas 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 thathepPplays 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.