Manipulation of intestinal epithelial cell function by the cell contact-dependent type III secretion systems of Vibrio parahaemolyticus

Abstract

Vibrio parahaemolyticus elicits gastroenteritis by deploying Type III Secretion Systems (TTSS) to deliver effector proteins into epithelial cells of the human intestinal tract. The bacteria must adhere to the human cells to allow colonization and operation of the TTSS translocation apparatus bridging the bacterium and the host cell. This article first reviews recent advances in identifying the molecules responsible for intercellular adherence. V. parahaemolyticus possesses two TTSS, each of which delivers an exclusive set of effectors and mediates unique effects on the host cell. TTSS effectors primarily target and alter the activation status of host cell signaling proteins, thereby bringing about changes in the regulation of cellular behavior. TTSS1 is responsible for the cytotoxicity of V. parahaemolyticus, while TTSS2 is necessary for the enterotoxicity of the pathogen. Recent publications have elucidated the function of several TTSS effectors and their importance in the virulence of the bacterium. This review will explore the ability of the TTSS to manipulate activities of human intestinal cells and how this modification of cell function favors bacterial colonization and persistence of V. parahaemolyticus in the host.

CRISPR/Cas9 Screens Reveal Requirements for Host Cell Sulfation and Fucosylation in Bacterial Type III Secretion System-Mediated Cytotoxicity

“…We created mutants lacking one or more of the 3 previously described V. parahaemolyticus adhesin-encoding genes ( mam7 , mshA1 and vpadF ) (Boyd, 2014) that have been implicated in T3SS1-killing to test whether they interact with sulfated compounds and contribute to the sulfation-dependent adhesion of the pathogen to host cells. MshA1 has been reported to bind both sulfated and non-sulfated glycans, while MAM7 and VpadF are reported to bind fibrinogen and/or fibronectin.…”

Vibrio parahaemolyticus virulence determinants

“…In immune-competent individuals, the illness is self-limiting and resolves itself within about 3 days. The symptoms include diarrhea with abdominal cramps, nausea, vomiting, low-grade fever, and occasional bloody diarrhea [8][9][10]. In immunocompromised individuals and those with certain underlying medical conditions, such as liver disease, diabetes, and cancer, V. parahaemolyticus can cross the intestinal barriers and reach the blood vessels, which leads to systemic spread of bacteria, a condition known as septicemia.…”

“…Adhesion occurs when adhesive molecules expressed on the bacterial surface bind to host surface receptors. Bacterial adhesins range from single monomeric proteins to multimeric complexes that may work in concert to yield a multivalent interaction between pathogen and host [8,34]. The following section will discuss in more detail the contribution of the capsular polysaccharide, the mannose-sensitive hemagglutinin (MSHA) Type IV pilus, and the multivalent adhesion molecule 7 (MAM7) to bacteria-host binding and their implications for pathogenicity.…”

“…Due to the global dissemination of the bacterium, the consumption of raw or undercooked seafood contaminated with V. parahaemolyticus has become the leading cause of seafood-borne acute gastroenteritis [8]. In immune-competent individuals, the illness is self-limiting and resolves itself within about 3 days.…”

Quorum Sensing Regulators Are Required for Metabolic Fitness in Vibrio parahaemolyticus

“…The completed genome sequence of V. parahaemolyticus RIMD2210633, an O3:K6 serotype associated with pandemic disease, demonstrated the presence of two type III secretion systems (T3SS-1 and T3SS-2), one on each chromosome, which led to the identification of several effector proteins associated with inflammatory diarrhea (6)(7)(8). Studies have shown that T3SS-2 is the major contributing factor to enterotoxicity and that inflammatory diarrhea and intestinal epithelium cell disruption are dependent upon a functional T3SS-2 (9)(10)(11)(12).…”