A Burkholderia Type VI Effector Deamidates Rho GTPases to Activate the Pyrin Inflammasome and Trigger Inflammation

• Published in: Cell host & microbe 2016-05, Vol.19 (5), p.664-674
• Main Authors: Aubert, Daniel F., Xu, Hao, Yang, Jieling, Shi, Xuyan, Gao, Wenqing, Li, Lin, Bisaro, Fabiana, Chen, She, Valvano, Miguel A., Shao, Feng
• Format: Article
• Language: English
• Subjects: Actin Cytoskeleton - drug effects; Actin Cytoskeleton - metabolism; Animals; Bacterial Proteins - metabolism; Burkholderia cenocepacia - enzymology; Burkholderia cenocepacia - genetics; Burkholderia cenocepacia - immunology; Burkholderia cenocepacia - metabolism; Burkholderia Infections - enzymology; Burkholderia Infections - immunology; Burkholderia Infections - metabolism; Caspase 1 - metabolism; Cell Line; HEK293 Cells; Humans; Inflammasomes - metabolism; Inflammation - enzymology; Inflammation - immunology; Inflammation - metabolism; Mice; Mice, Inbred C57BL; Pneumonia - enzymology; Pneumonia - immunology; Pyrin - immunology; Pyrin - metabolism; rho GTP-Binding Proteins - immunology; rho GTP-Binding Proteins - metabolism; rhoA GTP-Binding Protein - metabolism
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2016.04.004

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. [Display omitted] •B. cenocepacia employs a type VI effector, TecA, to disrupt the host actin cytoskeleton•TecA and its homologs inactivate Rho GTPases by deamidating a conserved asparagine•TecA deamidation of RhoA activates the Pyrin inflammasome in vitro and in vivo•Detection of TecA by Pyrin protects mice from lethal B. cenocepacia infection Burkholderia cenocepacia is highly proinflammatory and causes severe lung infection in cystic fibrosis patients. Aubert et al. identify a type VI effector, TecA, in B. cenocepacia that disrupts macrophage actin cytoskeleton by deamidating Rho GTPases. The action of TecA is detected by the Pyrin inflammasome, which triggers inflammation in mice.