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The ubiquitin ligase TRIM27 functions as a host restriction factor antagonized by Mycobacterium tuberculosis PtpA

Jing Wang1, Jade L L Teng2, Dongdong Zhao1,3

  • 1CAS key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Scientific Reports
|October 5, 2016
PubMed

Insights

Mycobacterium tuberculosis (Mtb) infection is restricted by host protein TRIM27, which promotes immune responses. Mtb effector PtpA counteracts TRIM27, suggesting targeting their interaction could treat tuberculosis.

Area of Science:

  • Immunology
  • Microbiology
  • Molecular Biology

Background:

  • Innate immunity is vital for pathogen defense, with host restriction factors limiting viral replication.
  • Essential factors restricting Mycobacterium tuberculosis (Mtb) and their regulation during infection are poorly understood.
  • Mtb effector PtpA inhibits innate immunity by manipulating the host ubiquitin system.

Purpose of the Study:

  • Identify host factors restricting Mtb.
  • Investigate the role of PtpA-interacting proteins in antimycobacterial immunity.
  • Explore PtpA-TRIM27 interactions as a therapeutic target for tuberculosis.

Main Methods:

  • Co-immunoprecipitation to identify PtpA-interacting proteins.
  • Macrophage infection assays to assess TRIM27's role in Mtb restriction.
  • Western blotting and apoptosis assays to analyze signaling pathways (JNK/p38 MAPK).

Main Results:

  • TRIM27 was identified as a PtpA-interacting host protein with E3 ubiquitin ligase activity.
  • TRIM27 restricts Mtb survival in macrophages by enhancing innate immunity and apoptosis.
  • Mtb PtpA antagonizes TRIM27 by binding its RING domain, inhibiting JNK/p38 MAPK activation and apoptosis.

Conclusions:

  • TRIM27 acts as a host restriction factor against Mtb, promoting immune responses and apoptosis.
  • Mtb effector PtpA counteracts TRIM27's antimycobacterial activity.
  • Targeting the TRIM27-PtpA interface presents a potential therapeutic strategy for tuberculosis.

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