STRAIN-SPECIFIC VIRULENCE SIGNATURES OF CAMPYLOBACTER JEJUNI ASSOCIATED WITH WATERY VERSUS BLOODY DIARRHEA IN NEONATAL PIGLET MODEL

Campylobacter jejuni is the leading cause of bacterial gastroenteritis globally, presenting with either watery or bloody/inflammatory diarrhea. Despite this clinical variability, the underlying mechanisms driving these distinct diarrheal manifestations remain unclear. The neonatal piglet model provides a unique opportunity to investigate these differences using strains with defined disease manifestations. We evaluated ten C. jejuni strains previously shown to cause consistent diarrheal manifestations in neonatal piglets: five strains associated with watery diarrhea and five associated with bloody/inflammatory diarrhea. The study found significant strain to strain variation among most assays, but overall strains associated with bloody/inflammatory diarrhea exhibited significantly higher levels of epithelial cell invasion, intracellular survival, macrophage survivability, and disruption of intestinal barrier integrity compared to watery diarrhea strains. Notably, both groups produced similar levels of cytolethal distending toxin (CDT), and elicited comparable IL-8 responses. While both groups facilitated translocation of commensal E. coli, only bloody/inflammatory strains caused increased paracellular permeability, as shown by TEER and FITC-dextran assays. Variation in adherence was observed between groups depending on the cell line used. This study reveals that there is significant variation in the virulence phenotype of C. jejuni strains and identifies several characteristics consistently associated with a specific diarrheal manifestation group. These findings provide new insights into the strain-specific pathogenic mechanisms of C. jejuni, with implications for understanding host-pathogen interactions and informing targeted diagnostic and therapeutic strategies.