Bacteria‑host transcriptional response during intestinal epithelial cells infection by Klebsiella pneumoniae

Klebsiella pneumoniae (K. pneumoniae) is an opportunistic pathogen responsible for severe hospital and community infections. Despite intestinal infections caused by K. pneumoniae are relatively rare, most systemic infections originate from its initial colonization of the gastrointestinal tract. However, the understanding of how K. pneumoniae interacts with human hosts is limited. In this study, we employed dual RNA-seq to characterize the interactions between K. pneumoniae and human intestinal epithelial cell (Caco-2). Differential gene expression analysis highlighted 331 altered genes in K. pneumoniae and 173 in infected Caco-2 cells. KEGG analysis revealed enrichment of these host genes in the HIF-1 and PI3K-Akt signaling pathways. Notably, the host genes encoding REDD1, BHLHE40, ANKRD37 and NLRP3 exhibited significant upregulation upon infection. REDD1 expression was progressively induced during infection, both at the mRNA and protein levels (significantly at 2h and 4h infection). In addition, functional study showed that siRNA-mediated knock-down of REDD1 did not affect intestinal epithelial tight junction integrity. However, REDD1 was critical for facilitating the intracellular invasion of K. pneumoniae. Finally, we found that molybdenum cofactor biosynthesis protein of K. pneumoniae encoded by mogA may promote bacterial invasion through host REDD1. This study for the first time demonstrated the potential interaction between K. pneumoniae and human intestinal epithelium.