TBK1 helps activate HDAC3 to speed up removal of bacteria inside cells

Dynamic acetylation of the xenophagy receptor NDP52 at K202 is enhanced during Salmonella Typhimurium infection.

• Deacetylation of NDP52 increases its binding affinity to ATG8 family proteins, which aids in pathogen degradation.
• The acetyltransferase CREBBP/KAT3A and deacetylase HDAC3 regulate the acetylation status of NDP52.
• Innate immune kinase TBK1 stabilizes HDAC3 by phosphorylating it, linking innate immunity to the xenophagy process.
• Liver-specific overexpression of deacetylation-mimetic NDP52^K202R in mice leads to reduced Salmonella Typhimurium burden and less liver damage.
• The findings suggest a regulatory role of NDP52 acetylation in antibacterial responses, indicating a potential target for therapeutic interventions.

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