Surgical Injury and Metabolic Stress Enhance the Virulence of the Human Opportunistic PathogenPseudomonas aeruginosa

Abstract

We have shown previously that the PA-I lectin of Pseudomonas aeruginosa plays a key role in gut-derived sepsis during surgical stress. The aims of this study were to determine if the intestinal tract lumen of a stressed host contained soluble factors that could induce the expression of PA-I. Mice were subjected to either 30% surgical hepatectomy or sham-laparotomy, and P. aeruginosa was introduced into the cecum. Twenty-four hours later, feces were recovered, and PA-I and exotoxin A were determined by real-time polymerase chain reaction (PCR). In reiterative experiments, fecal filtrates from both hepatectomy and sham-operated mice were tested for their ability to induce PA-I expression in cultures of P. aeruginosa. Finally, the media from cultured human intestinal epithelial (Caco-2) cells stressed with excess glutamine was tested for its ability to induce the expression of PA-I in cultures of P. aeruginosa. Both PA-I and exotoxin A mRNA were increased in vivo in the intestinal tract of mice subjected to 30% hepatectomy. Soluble fecal filtrates from hepatectomy mice induced PA-I in vitro. Media from epithelial cells exposed to excess glutamine alone induced PA-I expression. The intestinal environment of a stressed host contains soluble factors capable of inducing lethal virulence traits in human opportunistic pathogen P. aeruginosa.