Failure of Antisera to Thermostable Direct Hemolysin and Cholera Enterotoxin to Prevent Accumulation of Fluid Caused by Vibrio parahaemolyticus

Honda, Takeshi; Takeda, Yoshifumi; Miwatani, Toshio; Nakahara, Noriko

doi:10.1093/infdis/147.4.779

Cited by 12 publications

(10 citation statements)

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“…5A). These results agree with those of a previous study, which suggested that accumulation of fluid induced by V. parahaemolyticus is not directly related to TDH but may be caused by another factor(s) (14). It is possible that the predicted but as-yet-unknown factor(s) responsible for V. parahaemolyticus-induced enterotoxicity is an effector(s) injected by T3SS2.…”

Section: Discussionsupporting

confidence: 92%

Contribution of Vibrio parahaemolyticus Virulence Factors to Cytotoxicity, Enterotoxicity, and Lethality in Mice

Hiyoshi¹,

Kodama

Iida³

et al. 2010

Infect Immun

199

226

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Vibrio parahaemolyticus, one of the human-pathogenic vibrios, causes three major types of clinical illness: gastroenteritis, wound infections, and septicemia. Thermostable direct hemolysin (TDH) secreted by this bacterium has been considered a major virulence factor of gastroenteritis because it has biological activities, including cytotoxic and enterotoxic activities. Previous reports revealed that V. parahaemolyticus strain RIMD2210633, which contains tdh, has two sets of type III secretion system (T3SS) genes on chromosomes 1 and 2 (T3SS1 and T3SS2, respectively) and that T3SS1 is responsible for cytotoxicity and T3SS2 is involved in enterotoxicity, as well as in cytotoxic activity. However, the relative importance and contributions of TDH and the two T3SSs to V. parahaemolyticus pathogenicity are not well understood. In this study, we constructed mutant strains with nonfunctional T3SSs from the V. parahaemolyticus strain containing tdh, and then the pathogenicities of the wild-type and mutant strains were evaluated by assessing their cytotoxic activities against HeLa, Caco-2, and RAW 264 cells, their enterotoxic activities in rabbit ileal loops, and their lethality in a murine infection model. We demonstrated that T3SS1 was involved in cytotoxic activities against all cell lines used in this study, while T3SS2 and TDH had cytotoxic effects on a limited number of cell lines. T3SS2 was the major contributor to V. parahaemolyticus-induced enterotoxicity. Interestingly, we found that both T3SS1 and TDH played a significant role in lethal activity in a murine infection model. Our findings provide new indications that these virulence factors contribute to and orchestrate each distinct aspect of the pathogenicity of V. parahaemolyticus.Vibrio parahaemolyticus is a Gram-negative halophilic bacterium that inhabits estuarine and coastal waters and can be isolated from seafood (6,7,9). It causes acute gastroenteritis in humans after they consume contaminated raw or undercooked seafood. Although this microorganism is better known for causing gastroenteritis, it also can cause wound infections and septicemia (5,23,36).Most clinical isolates of V. parahaemolyticus from patients with diarrhea show ␤-hemolysis on Wagatsuma agar (37). This phenomenon is known as the Kanagawa phenomenon (KP) and is considered a good marker to distinguish between pathogenic and nonpathogenic V. parahaemolyticus strains (25, 37). Thermostable direct hemolysin (TDH), which is responsible for the KP (28, 43), has multiple biological activities, including hemolysis, enterotoxicity, cytotoxicity, and cardiotoxicity (11-13, 26, 29, 32, 34, 38). For this reason, TDH has been considered a major virulence factor of V. parahaemolyticus.Whole-genome sequencing of a KP-positive V. parahaemolyticus strain revealed that this strain contains two sets of gene clusters for the type III secretion system (T3SS), T3SS1 and T3SS2, one on each of its two chromosomes (21). T3SS gene clusters have been detected in numerous Gram-negative animal and plant pathogens, wh...

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Section: Discussionsupporting

confidence: 92%

Contribution of Vibrio parahaemolyticus Virulence Factors to Cytotoxicity, Enterotoxicity, and Lethality in Mice

Hiyoshi¹,

Kodama

Iida³

et al. 2010

Infect Immun

199

226

View full text Add to dashboard Cite

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“…Direct evidence for the role of these hemolysins in the pathogenesis of Vibrio infections has not been forthcoming. TDH-negative strains of V. parahaemolyticus produce fluid accumulation in rabbits comparable to that caused by TDHpositive strains, and the response is not affected by anti-TDH serum (9). In human volunteer studies, genetically engineered strains of V. cholerae 01 that produce the El Tor hemolysin but have deletions in either the A subunit or the A and B subunits of cholera toxin still produce mild diarrhea (19).…”

Section: Discussionmentioning

confidence: 99%

The extracellular cytolysin of Vibrio vulnificus: inactivation and relationship to virulence in mice

1991

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The ca. 51-kDa extracellular cytolysin of Vibrio vulnificus has been proposed as a virulence factor. We inactivated the structural gene for cytolysin in fully virulent, clinical V. vulnificus strains by both transposon mutagenesis and marker exchange techniques. Inactivation of the cytolysin did not affect virulence in our mouse models. The 50% lethal dose of cytolysin-negative strains was comparable to that of the cytolysin-positive parent strains after intraperitoneal inoculation with and without iron loading. Similar results were obtained after intradermal injection: cytolysin-positive and -negative strains had the same 50% lethal dose and caused comparable tissue damage. While we cannot say that the cytolysin has no effect on the pathogenesis of V. vulnificus infections, its role appears to be of much less importance than are other factors, such as encapsulation.

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“…18,19 Purified TDH induces intestinal fluid accumulation but only at extremely high doses (≥100 μg/1 mL of inoculum in a rabbit ileal loop). 18,100 Moreover, anti-TDH antibodies fail to neutralize the intestinal fluid accumulation induced by V. parahaemolyticus, 18,104 suggesting that secreted TDH is unnecessary for the intestinal fluid accumulation observed during infection. Recently, an unexpected role of TDH in the diarrhea-inducing activity of V. parahaemolyticus was described.…”

Section: For the Diarrhea-inducing Activity Through T3ss2mentioning

confidence: 99%

Advances on Vibrio parahaemolyticus research in the postgenomic era

Matsuda

Hiyoshi

Tandhavanant

et al. 2020

Microbiology and Immunology

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Vibrio parahaemolyticus is a leading cause of seafood‐borne bacterial gastroenteritis in humans. Since its discovery in 1950, this bacterium has been isolated in widespread outbreaks and in sporadic cases of gastroenteritis worldwide. Although the exotoxin, thermostable direct hemolysin, had been the focus of extensive research on the pathogenicity of V. parahaemolyticus, the whole‐genome sequencing of a clinical isolate, RIMD2210633 strain, was a breakthrough in this field. The possession of two sets of gene clusters for type III secretion systems (T3SS1 and T3SS2) was unveiled by that genome project. T3SS is a protein export apparatus that delivers bacterial proteins, called effectors, directly into the host's cytosol, to disrupt host cell function. The subsequent studies have established that T3SS2, which is encoded in an 80 kb pathogenicity island called V. parahaemolyticus pathogenicity island (Vp‐PAI), is closely related to enteropathogenicity. Recent functional analyses of Vp‐PAI‐encoded genes revealed the sophisticated mechanisms in V. parahaemolyticus for sensing the intestinal environment and host cell contact, and a dozen T3SS2‐exported proteins encoded in Vp‐PAI. In this review, we summarize recent advances in V. parahaemolyticus research regarding the control of the expression of Vp‐PAI‐encoded genes, structural components and the secretory regulation of T3SS2, and the biological activities of T3SS2‐exported effectors. Thus, Vp‐PAI‐encoded T3SS2 becomes an important key in the postgenomic era to shed light on the enteropathogenic mechanism of V. parahaemolyticus.

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Failure of Antisera to Thermostable Direct Hemolysin and Cholera Enterotoxin to Prevent Accumulation of Fluid Caused by Vibrio parahaemolyticus

Cited by 12 publications

References 1 publication

Contribution of Vibrio parahaemolyticus Virulence Factors to Cytotoxicity, Enterotoxicity, and Lethality in Mice

Contribution of Vibrio parahaemolyticus Virulence Factors to Cytotoxicity, Enterotoxicity, and Lethality in Mice

The extracellular cytolysin of Vibrio vulnificus: inactivation and relationship to virulence in mice

Advances on Vibrio parahaemolyticus research in the postgenomic era

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