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

Objective To examine the effect of Pseudomonas aeruginosa on intestinal bar rier function and its lethal potential when introduced into the intestinal tract of mice. Summary Background Data The mere presence of P. aeruginosa in the intestina l tract of critically iii 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. Methods Transepithelial electrical resistance, a measure of tight junction permeability, was evaluated in Caco-2 intestinal epithelial cells cells api cally inoculated with live P, aeruginosa, exotoxin A, or purified PA-I lect in, an adhesin of P, aeruginosa. Lethality studies to P. aeruginosa were ca rried out in mice undergoing 30% surgical hepatectomy by injecting the bact eria or its various components directly into the cecum. Results Only cells exposed to P, aeruginosa or its PA-I lectin developed al terations 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 h epatectomy. Alterations in epithelial barrier function and death in mice we re prevented when Pseudomonas was pretreated with N-acetyl D-galactosamine (GalNAc), a binder of PA-I. Conclusions P. aeruginosa may act as a pathogen in the gastrointestinal tra ct, resulting in altered epithelial barrier function and death in a suscept ible host. The PA-I lectin of P. aeruginosa may play a key role in its path ogenicity to the intestinal epithelium by inducing a permeability defect to its cytotoxic exoproducts such as exotoxin A.