Coxiella burnetii inhibits host immunity by a protein phosphatase adapted from glycolysis.
Yong ZhangJiaqi FuShuxin LiuLidong WangJiazhang QiuErin J van SchaikJames E SamuelLei SongZhao-Qing LuoPublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
Coxiella burnetii is a bacterial pathogen that replicates within host cells by establishing a membrane-bound niche called the Coxiella -containing vacuole. Biogenesis of this compartment requires effectors of its Dot/Icm type IV secretion system. A large cohort of such effectors has been identified, but the function of most of them remain elusive. Here, by a cell-based functional screening, we identified the effector Cbu0513 (designated as CinF) as an inhibitor of NF-κB signaling. CinF is highly similar to a fructose-1,6-bisphosphate (FBP) aldolase/phosphatase present in diverse bacteria. Further study reveals that unlike its ortholog from Sulfolobus tokodaii , CinF does not exhibit FBP phosphatase activity. Instead, it functions as a protein phosphatase that specifically dephosphorylates and stabilizes IκBα. The IκBα phosphatase activity is essential for the role of CinF in C. burnetii virulence. Our results establish that C. burnetii utilizes a protein adapted from sugar metabolism to subvert host immunity.
Keyphrases
- protein kinase
- protein protein
- escherichia coli
- induced apoptosis
- signaling pathway
- staphylococcus aureus
- pseudomonas aeruginosa
- binding protein
- dendritic cells
- regulatory t cells
- small molecule
- cell therapy
- cell cycle arrest
- bone marrow
- inflammatory response
- antimicrobial resistance
- pi k akt
- toll like receptor
- nuclear factor
- energy transfer