Chloride secretion induced by thermostable direct haemolysin of Vibrio parahaemolyticus depends on colonic cell maturation

Takahashi, Akira; Iida, Tetsuya; Naim, Rochman; Naykaya, Yutaka; Honda, Takeshi

doi:10.1099/0022-1317-50-10-870

Cited by 26 publications

(12 citation statements)

References 22 publications

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“…The KP is caused by thermostable direct hemolysin (TDH) produced by this bacterium [6]. As purified TDH has multiple biological activities, including induction of fluid accumulation in the rabbit intestine, it has been considered a major virulence factor of V. parahaemolyticus [6]–[16].…”

Section: Introductionmentioning

confidence: 99%

Bile Acid-Induced Virulence Gene Expression of Vibrio parahaemolyticus Reveals a Novel Therapeutic Potential for Bile Acid Sequestrants

et al. 2010

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Vibrio parahaemolyticus, a bacterial pathogen, causes human gastroenteritis. A type III secretion system (T3SS2) encoded in pathogenicity island (Vp-PAI) is the main contributor to enterotoxicity and expression of Vp-PAI encoded genes is regulated by two transcriptional regulators, VtrA and VtrB. However, a host-derived inducer for the Vp-PAI genes has not been identified. Here, we demonstrate that bile induces production of T3SS2-related proteins under osmotic conditions equivalent to those in the intestinal lumen. We also show that bile induces vtrA-mediated vtrB transcription. Transcriptome analysis of bile-responsive genes revealed that bile strongly induces expression of Vp-PAI genes in a vtrA-dependent manner. The inducing activity of bile was diminished by treatment with bile acid sequestrant cholestyramine. Finally, we demonstrate an in vivo protective effect of cholestyramine on enterotoxicity and show that similar protection is observed in infection with a different type of V. parahaemolyticus or with non-O1/non-O139 V. cholerae strains of vibrios carrying the same kind of T3SS. In summary, these results provide an insight into how bacteria, through the ingenious action of Vp-PAI genes, can take advantage of an otherwise hostile host environment. The results also reveal a new therapeutic potential for widely used bile acid sequestrants in enteric bacterial infections.

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Section: Introductionmentioning

confidence: 99%

Bile Acid-Induced Virulence Gene Expression of Vibrio parahaemolyticus Reveals a Novel Therapeutic Potential for Bile Acid Sequestrants

et al. 2010

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“…This hemolysis is called the Kanagawa phenomenon (KP), which has been considered to be a useful marker to distinguish pathogenic from non-pathogenic strains [6], [7]. Thermostable direct hemolysin (TDH) is responsible for KP and purified TDH shows a number of biological effects, such as erythrocyte lysis, cytotoxicity and induction of fluid accumulation in an ileal loop model [6], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17]. Thus, TDH has been considered a major virulence factor of V. parahaemolyticus .…”

Section: Introductionmentioning

confidence: 99%

Two Regulators of Vibrio parahaemolyticus Play Important Roles in Enterotoxicity by Controlling the Expression of Genes in the Vp-PAI Region

et al. 2010

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Vibrio parahaemolyticus is an important pathogen causing food-borne disease worldwide. An 80-kb pathogenicity island (Vp-PAI), which contains two tdh (thermostable direct hemolysin) genes and a set of genes for the type III secretion system (T3SS2), is closely related to the pathogenicity of this bacterium. However, the regulatory mechanisms of Vp-PAI's gene expression are poorly understood. Here we report that two novel ToxR-like transcriptional regulatory proteins (VtrA and VtrB) regulate the expression of the genes encoded within the Vp-PAI region, including those for TDH and T3SS2-related proteins. Expression of vtrB was under control of the VtrA, as vector-expressed vtrB was able to recover a functional protein secretory capacity for T3SS2, independent of VtrA. Moreover, these regulatory proteins were essential for T3SS2-dependent biological activities, such as in vitro cytotoxicity and in vivo enterotoxicity. Enterotoxic activities of vtrA and/or vtrB deletion strains derived from the wild-type strain were almost absent, showing fluid accumulation similar to non-infected control. Whole genome transcriptional profiling of vtrA or vtrB deletion strains revealed that the expression levels of over 60 genes were downregulated significantly in these deletion mutant strains and that such genes were almost exclusively located in the Vp-PAI region. These results strongly suggest that VtrA and VtrB are master regulators for virulence gene expression in the Vp-PAI and play critical roles in the pathogenicity of this bacterium.

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“…This haemolysis is called the Kanagawa phenomenon (KP) and is induced by thermostable direct haemolysin (TDH) (Shirai et al ., 1990; Honda and Iida, 1993). Purified TDH causes a number of biological effects, including erythrocyte lysis, cardiotoxicity, disruption of the microtubule, induction of chloride ion secretion and production of fluid accumulation in the ileal loop model (Honda et al ., 1976a,b; Sakurai et al ., 1976; Goshima et al ., 1977; Honda and Iida, 1993; Tang et al ., 1995; 1997; Fabbri et al ., 1999; Raimondi et al ., 2000; Naim et al ., 2001; Takahashi et al ., 2001). Therefore, it has been considered that TDH is an important virulence factor produced by this bacterium.…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of VopT, a novel ADP-ribosyltransferase effector protein secreted via the Vibrio parahaemolyticus type III secretion system 2

et al. 2007

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SummaryVibrio parahaemolyticus strain RIMD2210633 has two sets of genes encoding two separate type III secretion systems (T3SSs), called T3SS1 and T3SS2. T3SS2 has a role in enterotoxicity and is present only in Kanagawa phenomenon-positive strains, which are pathogenic to humans. Accordingly, T3SS2 is considered to be closely related to V. parahaemolyticus human pathogenicity. Despite this, the biological actions of T3SS2 and the identity of the effector protein(s) secreted by this system have not been well understood. Here we report that T3SS2 induces a cytotoxic effect in Caco-2 and HCT-8 cells. Moreover, it was revealed that VPA1327 (vopT), a gene encoded within the proximity of T3SS2, is partly responsible for this cytotoxic effect. The VopT shows approximately 45% and 44% identity with the ADPribosyltransferase (ADPRT) domain of ExoT and ExoS, respectively, which are two T3SS-secreted effectors of Pseudomonas aeruginosa. T3SS2 was found to be necessary not only for the secretion, but also for the translocation of the VopT into host cells. We also demonstrate that VopT ADP-ribosylates Ras, a member of the low-molecular-weight G (LMWG) proteins both in vivo and in vitro. These results indicate that VopT is a novel ADPRT effector secreted via V. parahaemolyticus T3SS.

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Chloride secretion induced by thermostable direct haemolysin of Vibrio parahaemolyticus depends on colonic cell maturation

Abstract: Vibrio parahaemolyticus produces a thermostable direct haemolysin (TDH) that has been implicated in the pathogenesis of diarrhoeal disease caused by this organism.

Cited by 26 publications

References 22 publications

Bile Acid-Induced Virulence Gene Expression of Vibrio parahaemolyticus Reveals a Novel Therapeutic Potential for Bile Acid Sequestrants

Bile Acid-Induced Virulence Gene Expression of Vibrio parahaemolyticus Reveals a Novel Therapeutic Potential for Bile Acid Sequestrants

Two Regulators of Vibrio parahaemolyticus Play Important Roles in Enterotoxicity by Controlling the Expression of Genes in the Vp-PAI Region

Identification and characterization of VopT, a novel ADP-ribosyltransferase effector protein secreted via the Vibrio parahaemolyticus type III secretion system 2

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