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 had similar levels of adherence, 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. 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. Author SummaryCampylobacter jejuni is one of the most common bacterial causes of diarrhea worldwide, affecting millions each year. Infected individuals may experience either watery or bloody/inflammatory diarrhea, but the reasons why different strains cause different types of illness have remained a mystery. In this study, we used a neonatal piglet model, which accurately mimics human diarrheal disease, to investigate why certain C. jejuni strains cause more severe symptoms than others. We compared strains known to cause either watery or bloody diarrhea and found key differences in their ability to invade intestinal cells, survive inside immune cells, and damage the intestinal barrier. While both groups of strains could trigger inflammation and translocate E. coli through the intestinal lining, only the strains linked to bloody diarrhea caused significant barrier disruption and had increased intracellular survival. These findings reveal that different C. jejuni strains follow distinct paths during infection, which helps explain why they produce different symptoms. Unraveling these differences improves our overall understanding of Campylobacter pathogenesis that could lead to improved diagnostics and/or treatments to reduce the burden of campylobacteriosis around the world.