Klebsiella pneumoniae activates the TGF-β signaling pathway to adhere to and invade intestinal epithelial cells via enhancing TLL1 expression.

Klebsiella pneumoniae is a gram-negative bacterium that can cause many diseases in hospitals and communities. Intestinal K. pneumoniae infections are relatively rare. Most K. pneumoniae infections begin with the colonization of the gastrointestinal system. In this study, clinically isolated K. pneumoniae strains were used to infect intestinal epithelial Caco-2 cells to study the possible intestinal translocation mechanism of K. pneumoniae. We found that of the three K. pneumoniae strains tested, KP1821 exhibited the strongest adhesive and invasive abilities and that the adhesion to Caco-2 intestinal epithelial cells was affected by the acidic environment of the stomach. Transcriptome sequencing revealed the involvement of molecules associated with the extracellular matrix and cell adhesion, inflammatory response, calcium ion and transforming growth factor β (TGF-β) signaling pathways, and other abnormalities in biological processes and cell signaling pathways. Additionally, tolloid-like protein 1 (TLL1) was significantly upregulated. Knocking down TLL1 with shRNA significantly reduced KP1821's ability to invade and adhere to intestinal epithelial cells. TLL1 is involved in the activation of the TGF-β signaling pathway. Inhibition of this pathway using the inhibitor SB431542 induced significantly reduced adhesion and invasion capabilities of KP1821. Our findings demonstrate that TLL1 participates in K. pneumoniae adhesion and invasion of intestinal epithelial cells by activating the TGF-β signaling pathway.