The key role of Pseudomonas aeruginosa PA-I lectin on experimental gut-derived sepsis.

Abstract

To examine the effect of Pseudomonas aeruginosa on intestinal barrier function and its lethal potential when introduced into the intestinal tract of mice. The mere presence of P. aeruginosa in the intestinal tract of critically ill patients is associated with a threefold increase in death compared with matched cohorts without this pathogen. Whether this effect is a cause or a consequence of the critically ill state has not been previously addressed. Transepithelial electrical resistance, a measure of tight junction permeability, was evaluated in Caco-2 intestinal epithelial cells cells apically inoculated with live P. aeruginosa, exotoxin A, or purified PA-I lectin, an adhesin of P. aeruginosa. Lethality studies to P. aeruginosa were carried out in mice undergoing 30% surgical hepatectomy by injecting the bacteria or its various components directly into the cecum. Only cells exposed to P. aeruginosa or its PA-I lectin developed alterations in barrier function. P. aeruginosa or the combination of PA-I and exotoxin A was lethal to mice when injected into the cecum after partial hepatectomy. Alterations in epithelial barrier function and death in mice were prevented when Pseudomonas was pretreated with N-acetyl D-galactosamine (GalNAc), a binder of PA-I. P. aeruginosa may act as a pathogen in the gastrointestinal tract, resulting in altered epithelial barrier function and death in a susceptible host. The PA-I lectin of P. aeruginosa may play a key role in its pathogenicity to the intestinal epithelium by inducing a permeability defect to its cytotoxic exoproducts such as exotoxin A.