Protopanaxatriol Inhibits Listeria monocytogenes Infection Through a Multi-Target Virulence Suppression Strategy

Listeria monocytogenes (LM) infection relies on the synergistic effects of multiple virulence factors, including but not limited to flagella-mediated bacterial motility, listeriolysin O (LLO)-mediated immune evasion and inflammatory response, multiple virulence proteins anchored to the cell wall by SortaseA (SrtA), and internalin-mediated adhesion and invasion. These virulence factors are critical potential targets for developing anti-LM infection inhibitors. This study found that protopanaxatriol (ptt) significantly inhibited the adhesion and invasion of LM into epithelial cells potentially by interfering with internalin A/InlB (InlA/InlB)-mediated host–cell interactions and reducing the transcription of inlA and inlB. InlA was anchored to the cell wall by SrtA, and in silico analysis predicted that ptt may interact with key active residues of SrtA. Additionally, ptt was predicted to interact with LLO and inhibited its oligomer formation, resulting in a loss of its pore-forming activity. Flagella, SrtA, and LLO all affect bacterial biofilm formation; ptt inhibited the formation of biofilms and disrupted mature biofilm without affecting the growth of LM. Finally, ptt protected Galleria mellonella from LLO and LM by increasing survival and alleviating tissue damage. These results indicate that ptt shows excellent potential for the prevention and control of LM infection.