Contribution of the regulatory gene lasR to the pathogenesis of Pseudomonas aeruginosa infection of burned mice.

Abstract

Pseudomonas aeruginosa is a gram-negative opportunistic pathogen that causes severe infections in patients with burns. The P aeruginosa regulatory gene, lasR, regulates the expression of several virulence factors. The specific lasR isogenic mutant, PAO-R1, is defective in the synthesis of the 2 elastases (LasB and LasA) and produces low levels of exotoxin A and alkaline proteases. In this study, we used a burned mouse model to examine the role of lasR in the pathogenesis of P aeruginosa infections. We have examined the following aspects of P aeruginosa infections: 1) lethality to the burned mouse, 2) the dissemination within the body of the burned mouse, and 3) the local spread within the burned skin. In comparison with its parent strain, PAO1, PAO-R1 was less lethal. In addition, the numbers of PAO-R1 microorganisms recovered from the livers and spleens of the burned mice were less than those of PAO1. Furthermore, at 8 hours postinfection, equivalent numbers of PAO1 and PAO-R1 were detected at the inoculation site of the burned skin. However, only PAO1 microorganisms were detected at other sites of the burned skin. These results suggest that the lasR gene contributes (directly and indirectly) to the dissemination of P aeruginosa within the body of burned mice and its horizontal spread within the burned skin.