title: A Burkholderia Type VI Effector Deamidates Rho GTPases to Activate the Pyrin Inflammasome and Trigger Inflammation.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Western Ontario, London N6A 5C1, Canada.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Aubert
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jieling
authors.initials: J
authors.lastname: Yang
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Xuyan
authors.initials: X
authors.lastname: Shi
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Gao
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, Belfast BT9 7AE, UK.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Bisaro
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: She
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, University of Western Ontario, London N6A 5C1, Canada; Centre for Infection and Immunity, Queen's University Belfast, Belfast BT9 7AE, UK. Electronic address: m.valvano@qub.ac.uk.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Valvano
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China; National Institute of Biological Sciences, Beijing, Collaborative Innovation Center for Cancer Medicine, Beijing 102206, China. Electronic address: shaofeng@nibs.ac.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Shao
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D019121:Burkholderia Infections / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D057508:Burkholderia cenocepacia / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000201:enzymology / Q000276:immunology; D000071198:Pyrin / Q000276:immunology* / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D058847:Inflammasomes; D000071198:Pyrin; D020170:Caspase 1; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein