The receptor for advanced glycation end products is involved in Campylobacter jejuni cytolethal distending toxin intracellular trafficking

Abstract Cytolethal distending toxin (CDT) belongs to the genotoxin family and is closely related to Campylobacter jejuni -induced gastroenteritis. We recently reported that CDT triggers the danger-associated molecular pattern (DAMP)-associated signaling to exert deleterious effects on host cells. However, how CDT traffics in cells and the mechanism of CDT toxicity remain to be elucidated. In this study, we first reported that CDT interacts with receptor of advanced glycation end product (RAGE) and high mobility group box 1 (HMGB1) to enter the cells. Our results further indicate that CdtB transportation in cells through the dynamin-dependent endocytic pathway and lysosomes is involved in this process. Conversely, knockdown of RAGE using CRISPR-Cas9 resulted in a significant reduction in CDT-arrested cell cycles, indicating that RAGE is essential for CDT action in cells. The results of this study provide valuable insights into the pathogenic potential of CDT-producing bacteria, such as C. jejuni .