All authors approve of the EVP4593 manufacturer final manuscript.”
“Background Vibrio parahaemolyticus is a gram negative, halophilic bacterium that is found in warm marine environments, such as the commensal microflora of shellfish [1, 2]. The bacterium is a major food-borne pathogen that causes acute gastroenteritis following consumption of undercooked or raw shellfish, especially oysters. It has become an increasingly important pathogen during
the last decade as pandemic strains have emerged, most likely due to rising global temperatures and increased seafood consumption [3]. Approximately 50% of all cases of food-borne gastroenteritis in Southeast Asia are due to V. parahaemolyticus. It is one of the major health and economic problems in this region and the incidence of infection is rising throughout the United States, South America and Europe [4–8]. The bacterium infects the human intestinal epithelium causing diarrhoea, intestinal inflammation, abdominal cramps,
nausea, vomiting, headaches, selleck fever, chills and in some cases even death [8, 9]. Intestinal epithelial responses to V. parahaemolyticus infection include the activation of the inflammatory cascade, infiltration of phagocytes, epithelial cell damage, alterations in the structure and function of the tight junction barrier and the induction of fluid and electrolyte secretion [10, 11]. Sequencing of the genome of a pandemic strain of V. parahaemolyticus (RIMD2210633) in 2003 revealed the presence of two sets of genes encoding two separate Type III Secretion Systems, named TTSS1 and TTSS2 [12]. TTSS1 is present in
all V. parahaemolyticus strains and is involved in host cell cytotoxicity, while TTSS2 is responsible for Silibinin enterotoxicity (the ability to induce fluid accumulation in the intestine) and is predominantly found in pathogenic strains [13–15]. More recently a third TTSS, that is Lazertinib supplier closely related to TTSS2, was identified in trh-positive pathogenic strains of V. parahaemolyticus [16]. TTSS effector proteins are injected from the cytosol of bacterium directly into the cytoplasm of the host cell by means of a syringe-like delivery apparatus [17]. Once inside the host cells the effector proteins modify the activity of eukaryotic cell signalling pathways leading to changes in host cell behaviour that favour the colonization and persistence of bacteria in the host [18]. The Mitogen Activated Protein Kinases (MAPK) are a group of protein serine/threonine kinases that are activated in mammalian cells in response to a variety of extracellular stimuli and mediate signal transduction from the cell surface to the nucleus where they can alter the phosphorylation status of specific transcription factors [19–21]. Three major types of MAPK pathways have been reported so far in mammalian cells [19–21]. The ERK1/2 pathway is involved in cell proliferation and differentiation, whereas the JNK and p38 pathways are activated in response to stress stimuli [19–21].
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