Effector SpvB Disrupts Intestinal Epithelial Barrier Integrity for Bacterial Translocation.

are common enteric bacterial pathogens that infect both humans and animals. Intestinal epithelial barrier, formed by a single layer of epithelial cells and apical junctional complex (AJC), plays a crucial role in host defense against enteric pathogens to prevent bacterial translocation. However, the underlying mechanisms of intestinal epithelial barrier dysfunction caused by are poorly understood. It is found that a locus termed plasmid virulence () gene exists extensively in clinically important serovars. SpvB is a key effector encoded within this locus, and closely related to pathogenicity such as interfering with autophagy and iron homeostasis. To investigate the interaction between SpvB and intestinal epithelial barrier and elucidate the underlying molecular mechanism, we used the typical foodborne disease agent serovar Typhimurium () carrying or not to construct infection models and . C57BL/6 mice were orally challenged with wild-type strain SL1344 or -deficient mutant strain SL1344-Δ. Caco-2 cell monolayer model, as a widely used model to mimic the human intestinal epithelium , was infected with SL1344, SL1344-Δ, or complementary strain SL1344-c-Δ, respectively. The results showed that SpvB enhanced bacterial pathogenicity during infection , and contributed to intestinal epithelial barrier dysfunction in both infection systems. This SpvB-mediated barrier dysfunction was attributed to the cellular redistribution of Claudin-1, Occludin, and E-cadherin junctional proteins. Moreover, by using pharmacological inhibitors, we found that F-actin rearrangement and suppression of protein kinase C (PKC) signaling pathway were involved in SpvB-mediated barrier dysfunction. In conclusion, the study reveals the contribution of effector SpvB to the dysfunction of intestinal epithelial barrier integrity, which facilitates bacterial translocation the paracellular route to promote systemic dissemination. Our findings broaden the understanding of host-pathogen interactions in salmonellosis, and provide new strategies for the therapy in limiting bacterial dissemination during infection.