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

Summary: 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...

Full description

Bibliographic Details
Main Authors: Xuan Wu, Lantian Zhou, Chen Ye, Zhenzhong Zha, Chuchu Li, Chao Feng, Yue Zhang, Qian Jin, Jianyi Pan
Format: Article
Language:English
Published: Elsevier 2023-10-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124723012731
_version_ 1827792694693330944
author Xuan Wu
Lantian Zhou
Chen Ye
Zhenzhong Zha
Chuchu Li
Chao Feng
Yue Zhang
Qian Jin
Jianyi Pan
author_facet Xuan Wu
Lantian Zhou
Chen Ye
Zhenzhong Zha
Chuchu Li
Chao Feng
Yue Zhang
Qian Jin
Jianyi Pan
author_sort Xuan Wu
collection DOAJ
description Summary: 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.
first_indexed 2024-03-11T18:06:49Z
format Article
id doaj.art-0eeba7b3352c4626a8d6498b6596c85d
institution Directory Open Access Journal
issn 2211-1247
language English
last_indexed 2024-03-11T18:06:49Z
publishDate 2023-10-01
publisher Elsevier
record_format Article
series Cell Reports
spelling doaj.art-0eeba7b3352c4626a8d6498b6596c85d2023-10-17T04:07:02ZengElsevierCell Reports2211-12472023-10-014210113261Destruction of self-derived PAMP via T3SS2 effector VopY to subvert PAMP-triggered immunity mediates Vibrio parahaemolyticus pathogenicityXuan Wu0Lantian Zhou1Chen Ye2Zhenzhong Zha3Chuchu Li4Chao Feng5Yue Zhang6Qian Jin7Jianyi Pan8Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaZhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaZhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaZhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaZhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaZhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaZhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaZhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaZhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723012731CP: Microbiology
spellingShingle Xuan Wu
Lantian Zhou
Chen Ye
Zhenzhong Zha
Chuchu Li
Chao Feng
Yue Zhang
Qian Jin
Jianyi Pan
Destruction of self-derived PAMP via T3SS2 effector VopY to subvert PAMP-triggered immunity mediates Vibrio parahaemolyticus pathogenicity
Cell Reports
CP: Microbiology
title Destruction of self-derived PAMP via T3SS2 effector VopY to subvert PAMP-triggered immunity mediates Vibrio parahaemolyticus pathogenicity
title_full Destruction of self-derived PAMP via T3SS2 effector VopY to subvert PAMP-triggered immunity mediates Vibrio parahaemolyticus pathogenicity
title_fullStr Destruction of self-derived PAMP via T3SS2 effector VopY to subvert PAMP-triggered immunity mediates Vibrio parahaemolyticus pathogenicity
title_full_unstemmed Destruction of self-derived PAMP via T3SS2 effector VopY to subvert PAMP-triggered immunity mediates Vibrio parahaemolyticus pathogenicity
title_short Destruction of self-derived PAMP via T3SS2 effector VopY to subvert PAMP-triggered immunity mediates Vibrio parahaemolyticus pathogenicity
title_sort destruction of self derived pamp via t3ss2 effector vopy to subvert pamp triggered immunity mediates vibrio parahaemolyticus pathogenicity
topic CP: Microbiology
url http://www.sciencedirect.com/science/article/pii/S2211124723012731
work_keys_str_mv AT xuanwu destructionofselfderivedpampviat3ss2effectorvopytosubvertpamptriggeredimmunitymediatesvibrioparahaemolyticuspathogenicity
AT lantianzhou destructionofselfderivedpampviat3ss2effectorvopytosubvertpamptriggeredimmunitymediatesvibrioparahaemolyticuspathogenicity
AT chenye destructionofselfderivedpampviat3ss2effectorvopytosubvertpamptriggeredimmunitymediatesvibrioparahaemolyticuspathogenicity
AT zhenzhongzha destructionofselfderivedpampviat3ss2effectorvopytosubvertpamptriggeredimmunitymediatesvibrioparahaemolyticuspathogenicity
AT chuchuli destructionofselfderivedpampviat3ss2effectorvopytosubvertpamptriggeredimmunitymediatesvibrioparahaemolyticuspathogenicity
AT chaofeng destructionofselfderivedpampviat3ss2effectorvopytosubvertpamptriggeredimmunitymediatesvibrioparahaemolyticuspathogenicity
AT yuezhang destructionofselfderivedpampviat3ss2effectorvopytosubvertpamptriggeredimmunitymediatesvibrioparahaemolyticuspathogenicity
AT qianjin destructionofselfderivedpampviat3ss2effectorvopytosubvertpamptriggeredimmunitymediatesvibrioparahaemolyticuspathogenicity
AT jianyipan destructionofselfderivedpampviat3ss2effectorvopytosubvertpamptriggeredimmunitymediatesvibrioparahaemolyticuspathogenicity