A Novel Mouse Model of Enteric <named-content content-type="genus-species">Vibrio parahaemolyticus</named-content> Infection Reveals that the Type III Secretion System 2 Effector VopC Plays a Key Role in Tissue Invasion and Gastroenteritis

ABSTRACT The Gram-negative marine bacterium Vibrio parahaemolyticus is a common cause of infectious gastroenteritis due to the ingestion of contaminated seafood. Most virulent V. parahaemolyticus strains encode two type III secretion systems (T3SS1 and T3SS2); however, the roles they and their trans...

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Autores principales:	Hyungjun Yang, Marcela de Souza Santos, Julia Lee, Hong T. Law, Suneeta Chimalapati, Elena F. Verdu, Kim Orth, Bruce A. Vallance
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	T3SS Vibrio parahaemolyticus gastroenteritis in vivo model pathogenesis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7b754ce794bd415581ef5d7587332ed1
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spelling	oai:doaj.org-article:7b754ce794bd415581ef5d7587332ed12021-11-15T15:54:45ZA Novel Mouse Model of Enteric <named-content content-type="genus-species">Vibrio parahaemolyticus</named-content> Infection Reveals that the Type III Secretion System 2 Effector VopC Plays a Key Role in Tissue Invasion and Gastroenteritis10.1128/mBio.02608-192150-7511https://doaj.org/article/7b754ce794bd415581ef5d7587332ed12019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02608-19https://doaj.org/toc/2150-7511ABSTRACT The Gram-negative marine bacterium Vibrio parahaemolyticus is a common cause of infectious gastroenteritis due to the ingestion of contaminated seafood. Most virulent V. parahaemolyticus strains encode two type III secretion systems (T3SS1 and T3SS2); however, the roles they and their translocated effectors play in causing intestinal disease remain unclear. While studies have identified T3SS1 effectors as responsible for killing epithelial cells in culture, the T3SS2 effectors caused massive epithelial cell disruption in a rabbit ileal loop model. Additional models are thus needed to clarify the pathogen-host interactions that drive V. parahaemolyticus-associated gastroenteritis. Germfree mice were infected with a pathogenic clinical isolate of V. parahaemolyticus, RIMD2210633 (RIMD). The pathogen was found to adhere to as well as invade the cecal mucosa, accompanied by severe inflammation and dramatic mucosal damage, including widespread sloughing of infected epithelial cells. Mice infected with a V. parahaemolyticus strain lacking the T3SS1 (POR2) also developed severe pathology, similar to that seen with RIMD. In contrast, the ΔT3SS2 strain (POR3) appeared unable to invade the intestinal mucosa or cause any mucosal pathology. Confirming a role for TS332 effectors, a strain expressing the T3SS2 but lacking VopC (POR2ΔvopC), a T3SS2 effector implicated in epithelial cell invasion in culture, was strongly attenuated in invading the intestinal mucosa and in causing gastroenteritis, although infection with this mutant resulted in more pathology than the ΔT3SS2 strain. We thus present an experimental system that enables further characterization of T3SS effectors as well as the corresponding host inflammatory response involved in the gastroenteritis caused by invasive V. parahaemolyticus. IMPORTANCE Vibrio parahaemolyticus causes severe gastroenteritis following consumption of contaminated seafood. Global warming has allowed this pathogen to spread worldwide, contributing to recent outbreaks. Clinical isolates are known to harbor an array of virulence factors, including T3SS1 and T3SS2; however, the precise role these systems play in intestinal disease remains unclear. There is an urgent need to improve our understanding of how V. parahaemolyticus infects hosts and causes disease. We present a novel mouse model for this facultative intracellular pathogen and observe that the T3SS2 is essential to pathogenicity. Moreover, we show that the T3SS2 effector VopC, previously shown to be a Rac and Cdc42 deamidase that facilitates bacterial uptake by nonphagocytic cells, also plays a key role in the ability of V. parahaemolyticus to invade the intestinal mucosa and cause gastroenteritis. This experimental model thus provides a valuable tool for future elucidation of virulence mechanisms used by this facultative intracellular pathogen during in vivo infection.Hyungjun YangMarcela de Souza SantosJulia LeeHong T. LawSuneeta ChimalapatiElena F. VerduKim OrthBruce A. VallanceAmerican Society for MicrobiologyarticleT3SSVibrio parahaemolyticusgastroenteritisin vivo modelpathogenesisMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	T3SS Vibrio parahaemolyticus gastroenteritis in vivo model pathogenesis Microbiology QR1-502
spellingShingle	T3SS Vibrio parahaemolyticus gastroenteritis in vivo model pathogenesis Microbiology QR1-502 Hyungjun Yang Marcela de Souza Santos Julia Lee Hong T. Law Suneeta Chimalapati Elena F. Verdu Kim Orth Bruce A. Vallance A Novel Mouse Model of Enteric <named-content content-type="genus-species">Vibrio parahaemolyticus</named-content> Infection Reveals that the Type III Secretion System 2 Effector VopC Plays a Key Role in Tissue Invasion and Gastroenteritis
description	ABSTRACT The Gram-negative marine bacterium Vibrio parahaemolyticus is a common cause of infectious gastroenteritis due to the ingestion of contaminated seafood. Most virulent V. parahaemolyticus strains encode two type III secretion systems (T3SS1 and T3SS2); however, the roles they and their translocated effectors play in causing intestinal disease remain unclear. While studies have identified T3SS1 effectors as responsible for killing epithelial cells in culture, the T3SS2 effectors caused massive epithelial cell disruption in a rabbit ileal loop model. Additional models are thus needed to clarify the pathogen-host interactions that drive V. parahaemolyticus-associated gastroenteritis. Germfree mice were infected with a pathogenic clinical isolate of V. parahaemolyticus, RIMD2210633 (RIMD). The pathogen was found to adhere to as well as invade the cecal mucosa, accompanied by severe inflammation and dramatic mucosal damage, including widespread sloughing of infected epithelial cells. Mice infected with a V. parahaemolyticus strain lacking the T3SS1 (POR2) also developed severe pathology, similar to that seen with RIMD. In contrast, the ΔT3SS2 strain (POR3) appeared unable to invade the intestinal mucosa or cause any mucosal pathology. Confirming a role for TS332 effectors, a strain expressing the T3SS2 but lacking VopC (POR2ΔvopC), a T3SS2 effector implicated in epithelial cell invasion in culture, was strongly attenuated in invading the intestinal mucosa and in causing gastroenteritis, although infection with this mutant resulted in more pathology than the ΔT3SS2 strain. We thus present an experimental system that enables further characterization of T3SS effectors as well as the corresponding host inflammatory response involved in the gastroenteritis caused by invasive V. parahaemolyticus. IMPORTANCE Vibrio parahaemolyticus causes severe gastroenteritis following consumption of contaminated seafood. Global warming has allowed this pathogen to spread worldwide, contributing to recent outbreaks. Clinical isolates are known to harbor an array of virulence factors, including T3SS1 and T3SS2; however, the precise role these systems play in intestinal disease remains unclear. There is an urgent need to improve our understanding of how V. parahaemolyticus infects hosts and causes disease. We present a novel mouse model for this facultative intracellular pathogen and observe that the T3SS2 is essential to pathogenicity. Moreover, we show that the T3SS2 effector VopC, previously shown to be a Rac and Cdc42 deamidase that facilitates bacterial uptake by nonphagocytic cells, also plays a key role in the ability of V. parahaemolyticus to invade the intestinal mucosa and cause gastroenteritis. This experimental model thus provides a valuable tool for future elucidation of virulence mechanisms used by this facultative intracellular pathogen during in vivo infection.
format	article
author	Hyungjun Yang Marcela de Souza Santos Julia Lee Hong T. Law Suneeta Chimalapati Elena F. Verdu Kim Orth Bruce A. Vallance
author_facet	Hyungjun Yang Marcela de Souza Santos Julia Lee Hong T. Law Suneeta Chimalapati Elena F. Verdu Kim Orth Bruce A. Vallance
author_sort	Hyungjun Yang
title	A Novel Mouse Model of Enteric <named-content content-type="genus-species">Vibrio parahaemolyticus</named-content> Infection Reveals that the Type III Secretion System 2 Effector VopC Plays a Key Role in Tissue Invasion and Gastroenteritis
title_short	A Novel Mouse Model of Enteric <named-content content-type="genus-species">Vibrio parahaemolyticus</named-content> Infection Reveals that the Type III Secretion System 2 Effector VopC Plays a Key Role in Tissue Invasion and Gastroenteritis
title_full	A Novel Mouse Model of Enteric <named-content content-type="genus-species">Vibrio parahaemolyticus</named-content> Infection Reveals that the Type III Secretion System 2 Effector VopC Plays a Key Role in Tissue Invasion and Gastroenteritis
title_fullStr	A Novel Mouse Model of Enteric <named-content content-type="genus-species">Vibrio parahaemolyticus</named-content> Infection Reveals that the Type III Secretion System 2 Effector VopC Plays a Key Role in Tissue Invasion and Gastroenteritis
title_full_unstemmed	A Novel Mouse Model of Enteric <named-content content-type="genus-species">Vibrio parahaemolyticus</named-content> Infection Reveals that the Type III Secretion System 2 Effector VopC Plays a Key Role in Tissue Invasion and Gastroenteritis
title_sort	novel mouse model of enteric <named-content content-type="genus-species">vibrio parahaemolyticus</named-content> infection reveals that the type iii secretion system 2 effector vopc plays a key role in tissue invasion and gastroenteritis
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/7b754ce794bd415581ef5d7587332ed1
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A Novel Mouse Model of Enteric <named-content content-type="genus-species">Vibrio parahaemolyticus</named-content> Infection Reveals that the Type III Secretion System 2 Effector VopC Plays a Key Role in Tissue Invasion and Gastroenteritis

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