Contribution of quorum sensing to the virulence of Pseudomonas aeruginosa in burn wound infections

The Pseudomonas aeruginosa quorum-sensing systems, las and rhl,control the production of numerous virulence factors, In this study, we have used the b urned-mouse model to examine the contribution of quorum-sensing systems to the pathogenesis of P. aeruginosa infections in burn wounds. Different quor um-sensing mutants of P. aeruginosa PAO1 that were defective in the lasR, l asI, or rhlI gene or both the lasI and rhlI genes were utilized. The follow ing parameters of the P. aeruginosa infection were examined: (i) lethality to the burned mouse, (ii) dissemination of the P. aeruginosa strain within the body of the infected mouse (by determining the numbers of CFU of P. aer uginosa within the liver and spleen), and (iii) spread of the P. aeruginosa strain within the burned skin (by determining the numbers of CFU of P, aer uginosa at the inoculation site and at a site about 15 mm from the inoculat ion site [distant site]), In comparison with that of PAO1, the in vivo viru lence of lasI, lasR, and rhlI mutants was significantly reduced. However, t he most significant reduction in in vivo virulence was seen with the lasI r hlI hll mutant. The numbers of CFU that were recovered from the livers, spl eens, and skin of mice infected with different mutants mere significantly l ower than those of PAO1, At 8 and 16 h post hum infection, comparable numbe rs of CFU of PAO1 and lasI and rhlI mutants were obtained from both the ino culation and distant sites of the burned skin of infected mice. In contrast , CPU of the lasR mutant and the lasI rhlI double mutant were recovered onl y from the inoculation site of infected mice at 8 and 16 h post burn infect ion. The ability of a plasmid carrying either the lasI or I ha gene or the lasI and rhlI genes to complement the defect of the lasI rhlI double mutant was also examined. The presence of any of these plasmids within the lasI r hlI double mutant significantly enhanced its in vivo virulence, as well as its ability to spread within the burned skin. These results suggest that th e quorum-sensing systems play an important role in the horizontal spread of P. aeruginosa within burned skin and in the dissemination of P. aeruginosa within the bodies of burned-and-infected mice and contributed to the overa ll virulence of P. aeruginosa in this animal model.