Expression of the soxR gene of Pseudomonas aeruginosa is inducible during infection of burn wounds in mice and is required to cause efficient bacteremia

Burn wounds are prone to infection by Pseudomonas aeruginosa, which is an o pportunistic pathogen causing various human diseases. During infection, the bacterium senses environmental changes and regulates the expression of gen es appropriate for survival. A purine-auxotrophic mutant of P. aeruginosa w as unable to replicate efficiently on burn wounds, suggesting that burn wou nds are purine-deficient environments. An in vivo expression technology bas ed on purEK gene expression was applied to the burned mouse infection model to isolate P. aeruginosa genes that are specifically induced during infect ion. Four such in vivo inducible (ivi) genetic loci were identified, includ ing the gene for a superoxide response regulator (soxR), the gene for a mal ate synthase G homologue (glcG), an antisense transcript of a putative regu lator responding to copper (copR), and an uncharacterized genetic locus. So xR of Escherichia coli is known to regulate genes involved in protecting th e bacterium against oxidative stress. The expression of soxR was proven to be highly inducible during the infection of burned mice and also inducible by treatment dth paraquat, which is a redox-cycling reagent generating intr acellular superoxide. The SoxR protein functions as an autorepressor in the absence of paraquat, whereas in the presence of paraquat, this autorepress ion is diminished. Furthermore, a soxR null mutant was shown to be much mor e sensitive than wild-type P. aeruginosa to macrophage-mediated killing. In support of this observation, a soxR nub mutant exhibited a significant del ay in causing systemic infections in the burned mice. Since most mortality in burn patients is caused by systemic infection, the defect in the ability to cause efficient bacteremia in burned mice suggests an important role of the soxR gene in the infection of burn wounds.