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

Abstract

Cyclic di-guanosine monophosphate (c-di-GMP) is a unique bacterial second messenger but is hijacked by host cells during bacterial infection as a pathogen-associated molecular pattern (PAMP) to trigger STING-dependent immune responses. Here, we show that upon infection, VopY, an effector of Vibrio parahaemolyticus, is injected into host cells by type III secretion system 2 (T3SS2), a secretion system unique to its pathogenic strains and indispensable for enterotoxicity. VopY is an EAL-domain-containing phosphodiesterase and is capable of hydrolyzing c-di-GMP. VopY expression in host cells prevents the activation of STING and STING-dependent downstream signaling triggered by c-di-GMP and, consequently, suppresses type I interferon immune responses. The presence of VopY in V. parahaemolyticus enables it to cause both T3SS2-dependent enterotoxicity and cytotoxicity. These findings uncover the destruction of self-derived PAMPs by injecting specific effectors to suppress PAMP-triggered immune responses as a unique strategy for bacterial pathogens to subvert immunity and cause disease.

• Authors: Xuan Wu, Lantian Zhou, Chen Ye, Zhenzhong Zha, Chuchu Li, Chao Feng, Yue Zhang, Qian Jin, Jianyi Pan
• Journal: Cell reports (Cell Rep) Vol. 42 Issue 10 Pg. 113261 (10 31 2023) ISSN: 2211-1247 [Electronic] United States
• PMID: 37847589 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Type III Secretion Systems
• Bacterial Proteins

Topics

• Vibrio parahaemolyticus (metabolism)
• Virulence
• Innate Immunity Recognition
• Type III Secretion Systems (metabolism)
• Bacterial Proteins (metabolism)