A Novel Mouse Model of EntericVibrio parahaemolyticusInfection Reveals that the Type III Secretion System 2 Effector VopC Plays a Key Role in Tissue Invasion and Gastroenteritis Academic Article uri icon

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  • ABSTRACTThe Gram-negative marine bacteriumVibrio parahaemolyticusis a common cause of infectious gastroenteritis due to the ingestion of contaminated seafood. Most virulentV. parahaemolyticusstrains 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 driveV. parahaemolyticus-associated gastroenteritis. Germfree mice were infected with a pathogenic clinical isolate ofV. 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 aV. parahaemolyticusstrain lacking the T3SS1 (POR2) also developed severe pathology, similar to that seen with RIMD. In contrast, theΔT3SS2strain (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 theΔT3SS2strain. 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 invasiveV. parahaemolyticus.IMPORTANCEVibrio parahaemolyticuscauses 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 howV. parahaemolyticusinfects 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 ofV. parahaemolyticusto 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 duringin vivoinfection.


  • Yang, Hyungjun
  • de Souza Santos, Marcela
  • Lee, Julia
  • Law, Hong T
  • Chimalapati, Suneeta
  • Verdu, Elena
  • Orth, Kim
  • Vallance, Bruce A

publication date

  • December 17, 2019

published in