Differential pathogenic contributions of tdh/trh genes in Vibrio parahaemolyticus revealed by rabbit and mice model comparative study.

Vibrio parahaemolyticus is a major cause of foodborne diarrhea, with virulence mainly attributed to thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH). To identify an animal model that closely mimics human pathology, this study established New Zealand infant rabbit and mice infection models to systematically compare pathological and immunological responses. Key parameters evaluated included clinical signs, intestinal colonization, histopathological damage, and multi-organ function indicators. Results showed that the infant rabbit model exhibited classical infection symptoms, including 55% diarrhea incidence and 40% mortality (8 h), along with marked intestinal swelling and excessive mucus secretion. In contrast, mice showed only transient behavioral changes (huddling/chill). Both models showed significant elevations in inflammatory cytokines (IL-1β, IL-6, TNF-α) and liver/kidney function markers (ALT, AST, BUN) (p < 0.05). However, the infant rabbit model demonstrated superior reproducibility of symptoms, consistency in pathological progression, and greater resemblance to human diarrheal disease compared to mice. Further virulence gene function analysis in the rabbit model revealed that TDH-positive strains induced more severe intestinal colonization, heightened inflammatory response (19.61% increase in IL-8), greater renal impairment (AST and BUN increased by 17.6% and 17.76%, respectively), and more pronounced cellular DNA damage compared to TRH-positive strains. This study not only established infant rabbits as a superior animal model for investigating the pathogenesis of Vibrio. parahaemolyticus, but also experimentally confirmed that TDH exerts a significantly stronger virulence effect than TRH. These findings provide essential data for virulence stratification and diarrheal disease prevention, and offer valuable insights for the development of preventive strategies against diarrheal diseases.