<i>Coxiella burnetii</i> inhibits host immunity by a protein phosphatase adapted from glycolysis.

Abstract

<i>Coxiella burnetii</i> is a bacterial pathogen that replicates within host cells by establishing a membrane-bound niche called the <i>Coxiella</i>-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 <i>Sulfolobus tokodaii</i>, 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 <i>C. burnetii</i> virulence. Our results establish that <i>C. burnetii</i> utilizes a protein adapted from sugar metabolism to subvert host immunity.