2. Academic Validation
  3. Pathogen hijacks programmed cell death signaling by arginine ADPR-deacylization of caspases

Pathogen hijacks programmed cell death signaling by arginine ADPR-deacylization of caspases

  • Mol Cell. 2022 May 19;82(10):1806-1820.e8. doi: 10.1016/j.molcel.2022.03.010.
Ting Peng 1,  Xinyuan Tao 2,  Zhujun Xia 2,  Shufan Hu 2,  Juan Xue 3,  Qiuyu Zhu 2,  Xing Pan 1,  Qiang Zhang 2,  Shan Li 4
Affiliations

Affiliations

  • 1 College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Institute of Infection and Immunity, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China; College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
  • 2 College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
  • 3 Institute of Infection and Immunity, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China.
  • 4 College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Institute of Infection and Immunity, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China; College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address: [email protected].
PMID: 35338844 DOI: 10.1016/j.molcel.2022.03.010
Abstract

Caspases are evolutionarily conserved cysteine proteases that are essential for regulating cell death and are involved in multiple development and disease processes, including immunity. Here, we show that the Bacterial type III secretion system (T3SS) effector CopC (Chromobacterium outer protein C) from the environmental pathogen Chromobacterium violaceum attacks Caspase-3/-7/-8/-9 by ADPR-deacylization to dysregulate programmed cell death, including Apoptosis, Necroptosis, and Pyroptosis. This modification involves ADP-ribosylation- and deamination-mediated cyclization on Arg207 of Caspase-3 by a mechanism that requires the eukaryote-specific protein Calmodulin (CaM), leading to inhibition of Caspase activity. The manipulation of cell death signaling by CopC is essential for the virulence of C. violaceum in a mouse Infection model. CopC represents a family of enzymes existing in taxonomically diverse bacteria associated with a wide spectrum of eukaryotes ranging from humans to Plants. The unique activity of CopC establishes a mechanism by which bacteria counteract host defenses through a previously unrecognized post-translational modification.

Keywords

ADP-ribosylation; ADPR-deacylization; Chromobacterium violaceum; caspase-3; caspase-8; necroptosis; new PTM; programmed cell death; pyroptosis; type III secretion system.

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