ST6GALNAC5 promotes Glaesserella parasuis infection by enhancing bacterial adhesion and amplifying host inflammatory responses.

Glaesserella parasuis (G. parasuis), the causative agent of Glässer's disease in pigs, relies on adhesion to host epithelial cells and induction of inflammation for pathogenesis. However, the potential role of ST6GALNAC5, a host sialyltransferase involved in glycan modification, in G. parasuis infection remains unclear. Using the porcine kidney epithelial cell line LLC-PK1, we investigated the function of the host sialyltransferase gene ST6GALNAC5 during G. parasuis infection. Infection significantly upregulated ST6GALNAC5 mRNA expression. CRISPR/Cas9-mediated knockout of ST6GALNAC5 reduced bacterial adhesion to and invasion of host cells. Compared to wild-type cells, ST6GALNAC5-KO cells exhibited higher proliferation and survival rates post-infection. Transcriptomic analysis revealed that ST6GALNAC5 knockout alone altered host cell pathways: DNA replication and cell cycle pathways were activated, while antigen processing and presentation and Toll-like receptor signaling pathways were suppressed. Consistently, upon infection, knockout cells showed significantly reduced expression of pro-inflammatory cytokines TNF-α, IL-8, IL-6, and IL-11. These findings demonstrate that ST6GALNAC5 promotes G. parasuis infection by enhancing bacterial adhesion, invasion and potentiating host inflammatory responses. Therefore, ST6GALNAC5 may serve as a potential host-directed target for controlling G. parasuis infection.