Triptolide clears Staphylococcus aureus infection by targeting XIAP to induce host apoptosis while preserving gut microbiota homeostasis [iBMDMs]

Host-directed therapy (HDT) has emerged as a promising alternative by modulating host immunity. With the multi-targeting and immunomodulatory properties, Traditional Chinese Medicine (TCM) monomers represent ideal candidates for HDT.

However, their ability to promote host immunity-mediated SA clearance remains largely unexplored. Here, we identified triptolide as a compound that facilitates intracellular clearance of SA and MRSA. Mechanistic studies revealed that triptolide directly binds to the X‑linked inhibitor of apoptosis protein (XIAP) to inhibit XIAP-caspase interaction, thereby releasing caspase inhibition and inducing apoptosis.