A Burkholderia Type VI Effector Deamidates Rho GTPases to Activate the Pyrin Inflammasome and Trigger Inflammation.
Burkholderia cenocepacia is an opportunistic pathogen of the cystic fibrosis lung that elicits a strong inflammatory response. B. cenocepacia employs a type VI secretion system (T6SS) to survive in macrophages by disarming Rho type GTPases, causing actin cytoskeletal defects. Here, we identified TecA, a non VgrG T6SS effector responsible for actin disruption. TecA and other bacterial homologs bear a cysteine protease like catalytic triad, which inactivates Rho GTPases by deamidating a conserved asparagine in the GTPase switch I region. RhoA deamidation induces caspase 1 inflammasome activation, which is mediated by the familial Mediterranean fever disease protein Pyrin. In mouse infection, the deamidase activity of TecA is necessary and sufficient for B. cenocepacia triggered lung inflammation and also protects mice from lethal B. cenocepacia infection. Therefore, Burkholderia TecA is a T6SS effector that modifies a eukaryotic target through an asparagine deamidase activity, which in turn elicits host cell death and inflammation through activation of the Pyrin inflammasome.
Cell host microbe