Agent-based model of epithelial host-pathogen interactions in anastomotic leak

Area of Science:

• Microbiology
• Computational Biology
• Gastroenterology

Background:

• Host-pathogen interactions (HPIs) are increasingly recognized for their role in gut biology.
• Understanding early postsurgical HPIs is key to addressing intestinal anastomotic leak.
• Agent-based modeling (ABM) offers a computational approach to study these complex interactions.

Purpose of the Study:

• To utilize an agent-based model (ABM) to investigate alterations in HPIs affecting epithelial barrier reestablishment.
• To explore mechanisms leading to anastomotic leak in the postsurgical gut.

Main Methods:

• Incorporated computational agents of Pseudomonas aeruginosa into a validated ABM of epithelial restitution.
• Simulated experiments assessed radiation effects on bacterial binding to epithelial cells.
• Investigated potential binding targets and mechanisms of bacterial-induced epithelial cell killing.

Main Results:

• Simulations mirrored in vitro binding patterns, identifying integrin-laminin associations as potential bacterial binding sites.
• Identified injected cytotoxin as the mechanism for bacterial-mediated tissue destruction leading to anastomotic leak.
• Genotyping confirmed the role of cytotoxin in virulent P. aeruginosa strains.

Conclusions:

• Agent-based modeling (ABM) serves as a valuable adjunct to traditional research methods.
• This study provides insights into the critical role of HPI in anastomotic leak pathogenesis.
• The findings highlight specific bacterial mechanisms contributing to postsurgical complications.