title: Agent-based model of epithelial host-pathogen interactions in anastomotic leak.
abstract: BACKGROUND
  There is a growing recognition of the significance of host-pathogen interactions (HPIs) in gut biology leading to a reassessment of the role of bacteria in intestinal anastomotic leak. Understanding the complexities of the early postsurgical gut HPI requires integrating knowledge of both epithelial and bacterial behaviors to generate hypotheses of potential mechanisms of interaction. Agent-based modeling is a computational method well suited to achieve this goal, and we use an agent-based model (ABM) to examine alterations in the HPI affecting reestablishment of the epithelial barrier that may subsequently lead to anastomotic leak.
  
  
  METHODS
  Computational agents representing Pseudomonas aeruginosa were added to a previously validated ABM of epithelial restitution. Simulated experiments were performed examining the effect of radiation on bacterial binding to epithelial cells, plausibility of putative binding targets, and potential mechanisms of epithelial cell killing by virulent bacteria.
  
  
  RESULTS
  Simulation experiments incorporating radiation effects on epithelial monolayers produced binding patterns akin to those seen in vitro and suggested that promotility integrin-laminin associations represent potential sites for bacterial binding and disruption of restitution. Simulations of potential mechanisms of epithelial cell killing suggested that an injected cytotoxin was the means by which virulent bacteria produced the tissue destruction needed to generate an anastomotic leak, a mechanism subsequently confirmed with genotyping of the virulent P aeruginosa strain.
  
  
  CONCLUSIONS
  This study emphasizes the utility of ABM as an adjunct to traditional research methods and provides insights into the potentially critical role of HPI in the pathogenesis of anastomotic leak.
authors.affiliation: Department of Surgery, University of Chicago, Chicago, Illinois.
authors.forename: Jordan R
authors.initials: JR
authors.lastname: Stern
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Olivas
authors.forename: Vesta
authors.initials: V
authors.lastname: Valuckaite
authors.forename: Olga
authors.initials: O
authors.lastname: Zaborina
authors.forename: John C
authors.initials: JC
authors.lastname: Alverdy
authors.forename: Gary
authors.initials: G
authors.lastname: An
mesh_terms: D000714:Anastomosis, Surgical; D057868:Anastomotic Leak / Q000503:physiopathology*; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D018988:Bacterial Translocation / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology; D002478:Cells, Cultured; D003198:Computer Simulation; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000382:microbiology / Q000473:pathology; D054884:Host-Pathogen Interactions / Q000502:physiology*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000382:microbiology* / Q000473:pathology; D008954:Models, Biological; D010641:Phenotype; D011552:Pseudomonas Infections / Q000503:physiopathology; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D051381:Rats
keywords: Agent-based modeling; Anastomotic leak; Bacterial virulence; Epithelial restitution; Host–pathogen interaction; Preoperative radiation; Pseudomonas aeruginosa