IucA gene contributes to the infectivity of hypervirulent Klebsiella pneumoniae in Caco-2 cell models

Hypervirulent Klebsiella pneumoniae (hvKP) causes lethal systemic infections following intestinal colonization, but the mechanisms underlying its translocation across the intestinal barrier remain unclear. In this study, we used Caco-2 cells as a model to investigate the role of the aerobactin siderophore-encoding gene iucA in the invasion process of hvKP. We observed that the wild-type (WT) hvKP strain exhibited significantly higher invasion rates than the iucA -deletion mutant ( ΔiucA ) at 2 and 4 hours post-infection (P < 0.05). Furthermore, only the WT strain penetrated dense Caco-2 monolayers, indicating that iucA is essential for traversing the intestinal mucosal barrier. Interaction transcriptomics revealed distinct host-pathogen dynamics: hvKP infection significantly activated pathways related to protein export and the bacterial secretion system; Caco-2 cells upregulated pentose/glucuronate interconversions, peroxisome activity, and TGF-β signaling but downregulated protein metabolism and autophagy; The transcriptional profile of Caco-2 monolayers was minimally altered by the presence or absence of iucA , suggesting that aerobactin’s role is primarily bacterial-centric. This study reveals the central role of iucA -mediated aerobactin synthesis in the invasion of the intestinal mucosal barrier by hvKP, providing important insights into the interaction between hvKP and intestinal epithelial cells.