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Cell Host Microbe. 2016 May 11;19(5):664-74. doi: 10.1016/j.chom.2016.04.004. Epub 2016 Apr 28.

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

Author information

1
Department of Microbiology and Immunology, University of Western Ontario, London N6A 5C1, Canada.
2
National Institute of Biological Sciences, Beijing 102206, China.
3
National Institute of Biological Sciences, Beijing 102206, China; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
4
Centre for Infection and Immunity, Queen's University Belfast, Belfast BT9 7AE, UK.
5
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.
6
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.

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.

PMID:
27133449
DOI:
10.1016/j.chom.2016.04.004
[Indexed for MEDLINE]
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