title: Pseudomonas aeruginosa potentiates the lethal effect of intestinal ischemia-reperfusion injury: the role of in vivo virulence activation.
abstract: BACKGROUND
  Experimental models of intestinal ischemia-reperfusion (IIR) injury are invariably performed in mice harboring their normal commensal flora, even though multiple IIR events occur in humans during prolonged intensive care confinement when they are colonized by a highly pathogenic hospital flora. The aims of this study were to determine whether the presence of the human pathogen Pseudomonas aeruginosa in the distal intestine potentiates the lethality of mice exposed to IIR and to determine what role any in vivo virulence activation plays in the observed mortality.
  
  
  METHODS
  Seven- to 9-week-old C57/BL6 mice were exposed to 15 minutes of superior mesenteric artery occlusion (SMAO) followed by direct intestinal inoculation of 1.0 × 10(6) colony-forming unit of P. aeruginosa PAO1 into the ileum and observed for mortality. Reiterative studies were performed in separate groups of mice to evaluate both the migration/dissemination pattern and in vivo virulence activation of intestinally inoculated strains using live photon camera imaging of both a constitutive bioluminescent P. aeruginosa PAO1 derivative XEN41 and an inducible reporter derivative of PAO1, the PAO1/lecA:luxCDABE that conditionally expresses the quorum sensing-dependent epithelial disrupting virulence protein PA 1 Lectin (PA-IL).
  
  
  RESULTS
  Mice exposed to 15 minutes of SMAO and reperfusion with intestinal inoculation of P. aeruginosa had a significantly increased mortality rate (p < 0.001) of 100% compared with <10% for sham-operated mice intestinally inoculated with P. aeruginosa without SMAO and IIR alone (<50%). Migration/dissemination patterns of P. aeruginosa in mice subjected to IIR demonstrated proximal migration of distally injected strains and translocation to mesenteric lymph nodes, liver, spleen, lung, and kidney. A key role for in vivo virulence expression of the barrier disrupting adhesin PA-IL during IIR was established since its expression was enhanced during IR and mutant strains lacking PA-IL displayed attenuated mortality.
  
  
  CONCLUSIONS
  The presence of intestinal P. aeruginosa potentiates the lethal effect of IIR in mice in part due to in vivo virulence activation of its epithelial barrier disrupting protein PA-IL.
authors: Department of Surgery, University of Chicago, Chicago, Illinois 60637, USA.
authors: David
authors: D
authors: Fink
authors: Kathleen
authors: K
authors: Romanowski
authors: Vesta
authors: V
authors: Valuckaite
authors: Trissa
authors: T
authors: Babrowski
authors: Moses
authors: M
authors: Kim
authors: Jeffrey B
authors: JB
authors: Matthews
authors: Donald
authors: D
authors: Liu
authors: Olga
authors: O
authors: Zaborina
authors: John C
authors: JC
authors: Alverdy
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D018988:Bacterial Translocation; D016009:Chi-Square Distribution; D004195:Disease Models, Animal; D007421:Intestine, Small / Q000098:blood supply* / Q000382:microbiology; D053208:Kaplan-Meier Estimate; D051379:Mice; D008810:Mice, Inbred C57BL; D011552:Pseudomonas Infections / Q000401:mortality / Q000503:physiopathology*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D011897:Random Allocation; D012016:Reference Values; D015427:Reperfusion Injury / Q000382:microbiology / Q000401:mortality* / Q000473:pathology; D018805:Sepsis / Q000382:microbiology / Q000401:mortality*; D016019:Survival Analysis; D014774:Virulence / Q000502:physiology