Destruction of self-derived PAMP via T3SS2 effector VopY to subvert PAMP-triggered immunity mediates Vibrio

Xuan Wu1, Lantian Zhou1, Chen Ye1

  • 1Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.

Cell Reports
|October 17, 2023
PubMed

Insights

Vibrio parahaemolyticus uses VopY to destroy cyclic di-guanosine monophosphate (c-di-GMP), a host immune signal. This bacterial strategy suppresses immune responses, enabling infection and disease.

Area of Science:

  • Microbiology
  • Immunology
  • Bacterial Pathogenesis

Background:

  • Cyclic di-guanosine monophosphate (c-di-GMP) acts as a bacterial second messenger.
  • Host cells recognize c-di-GMP as a pathogen-associated molecular pattern (PAMP) to activate STING-dependent immune responses.
  • Bacterial pathogens have evolved mechanisms to evade host immunity.

Purpose of the Study:

  • To investigate the role of Vibrio parahaemolyticus effector VopY in subverting host immunity.
  • To understand how VopY interferes with c-di-GMP-mediated immune signaling.
  • To elucidate the contribution of VopY to V. parahaemolyticus virulence.

Main Methods:

  • Investigated VopY's phosphodiesterase activity against c-di-GMP.
  • Assessed VopY's impact on STING activation and downstream signaling in host cells.
  • Evaluated the role of VopY and type III secretion system 2 (T3SS2) in V. parahaemolyticus enterotoxicity and cytotoxicity.

Main Results:

  • VopY, delivered by T3SS2, hydrolyzes host c-di-GMP.
  • VopY inhibits STING activation and suppresses type I interferon responses.
  • VopY contributes to both T3SS2-dependent enterotoxicity and cytotoxicity of V. parahaemolyticus.

Conclusions:

  • V. parahaemolyticus employs VopY to degrade host c-di-GMP, a key immune-triggering molecule.
  • Bacterial effector-mediated destruction of self-derived PAMPs is a novel immune evasion strategy.
  • This mechanism facilitates bacterial pathogenesis by suppressing PAMP-triggered immunity.

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