Gut-derived sepsis occurs when the right pathogen with the right virulencegenes meets the right host - Evidence for in vivo virulence expression in Pseudomonas aeruginosa

Objective To define the putative role of the PA-I lectin/adhesin, a binding protein of Pseudomonas aeruginosa, on lethal gut-derived sepsis after surg ical stress, and to determine if this protein is expressed in vivo in respo nse to physical and chemical changes in the local microenvironment of the i ntestinal tract after surgical stress. Summary Background Data Previous work from the authors' laboratory has esta blished that lethal gut-derived sepsis can be induced after the introductio n of P. aeruginosa into the cecum of mice after a 30% hepatectomy. This eff ect does not occur when P. aeruginosa is introduced into the cecum of sham operated control mice. Previous experiments further established that the me chanism of this effect is due to the presence of the PA-I lectin/adhesin of P. aeruginosa, which induces a permeability defect to a lethal cytotoxin o f P. aeruginosa, exotoxin A. Methods Three strains of P. aeruginosa, one lacking functional PA-I, were t ested in two complementary systems to assess virulence. Strains were tested for their ability to adhere to and alter the permeability of cultured huma n colon epithelial cells, and for their ability to induce mortality when in jected into the cecum of mice after a 30% hepatectomy. To determine if PA-I is "in vivo expressed" when present in the cecal environment after hepatec tomy, strains were retrieved from the cecum of sham-operated and hepatectom y-treated mice 24 and 48 hours after their introduction into the cecum and their PA-I expression was assessed. Results Results indicated that PA-I plays a putative role in lethal gut-der ived sepsis in the mouse, because strains lacking functional PA-I had an at tenuated effect on cultured human epithelial cells, and were nonlethal when injected into the cecum of mice after 30% surgical hepatectomy. Furthermor e, surgical stress in the form of hepatectomy significantly altered the int estinal microenvironment, resulting in an increase in luminal norepinephrin e associated with an increase in PA-I expression in retrieved strains of P. aeruginosa. Co-incubation of P. aeruginosa with norepinephrine increased P A-I expression in vitro, suggesting that norepinephrine plays a role in the observed response in vivo. Conclusions Lethal gut-derived sepsis may occur when intestinal pathogens e xpress virulence determinants in response to environmental signals indicati ng host stress. In this regard, the PA-I lectin/adhesin of P. aeruginosa ap pears to be a specific example of in vivo virulence expression in colonizin g pathogens in the intestinal tract in response to surgical stress.