title: Gut-derived sepsis occurs when the right pathogen with the right virulence genes meets the right host: evidence for in vivo virulence expression in Pseudomonas aeruginosa.
abstract: OBJECTIVE
  To define the putative role of the PA-I lectin/adhesin, a binding protein of Pseudomonas aeruginosa, on lethal gut-derived sepsis after surgical stress, and to determine if this protein is expressed in vivo in response to physical and chemical changes in the local microenvironment of the intestinal tract after surgical stress.
  
  
  BACKGROUND
  Previous work from the authors' laboratory has established that lethal gut-derived sepsis can be induced after the introduction of P. aeruginosa into the cecum of mice after a 30% hepatectomy. This effect does not occur when P. aeruginosa is introduced into the cecum of sham operated control mice. Previous experiments further established that the mechanism 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 of P. aeruginosa, exotoxin A.
  
  
  METHODS
  Three strains of P. aeruginosa, one lacking functional PA-I, were tested in two complementary systems to assess virulence. Strains were tested for their ability to adhere to and alter the permeability of cultured human colon epithelial cells, and for their ability to induce mortality when injected 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 hepatectomy, strains were retrieved from the cecum of sham-operated and hepatectomy-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-derived sepsis in the mouse, because strains lacking functional PA-I had an attenuated effect on cultured human epithelial cells, and were nonlethal when injected into the cecum of mice after 30% surgical hepatectomy. Furthermore, surgical stress in the form of hepatectomy significantly altered the intestinal microenvironment, resulting in an increase in luminal norepinephrine associated with an increase in PA-I expression in retrieved strains of P. aeruginosa. Co-incubation of P. aeruginosa with norepinephrine increased PA-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 express virulence determinants in response to environmental signals indicating host stress. In this regard, the PA-I lectin/adhesin of P. aeruginosa appears to be a specific example of in vivo virulence expression in colonizing pathogens in the intestinal tract in response to surgical stress.
authors.affiliation: Department of Surgery, University of Chicago, Chicago, Illinois 60637, USA. jalverdy@surgery.bsd.uchicago.edu
authors.forename: J
authors.initials: J
authors.lastname: Alverdy
authors.forename: C
authors.initials: C
authors.lastname: Holbrook
authors.forename: F
authors.initials: F
authors.lastname: Rocha
authors.forename: L
authors.initials: L
authors.lastname: Seiden
authors.forename: R L
authors.initials: RL
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Musch
authors.forename: E
authors.initials: E
authors.lastname: Chang
authors.forename: D
authors.initials: D
authors.lastname: Ohman
authors.forename: S
authors.initials: S
authors.lastname: Suh
mesh_terms: D018829:Adhesins, Bacterial / Q000502:physiology*; D000818:Animals; D001422:Bacterial Adhesion; D018988:Bacterial Translocation; D002432:Cecum / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000502:physiology; D006498:Hepatectomy; D006801:Humans; D037102:Lectins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity* / Q000502:physiology; D018805:Sepsis / Q000382:microbiology*; D013312:Stress, Physiological / Q000382:microbiology; D014774:Virulence / Q000235:genetics
chemical_list: D018829:Adhesins, Bacterial; D037102:Lectins