Vibrio cholerae: Cholera toxin

Broeck, Davy Vanden; Horvath, Caroline A.J.; Wolf, M.

doi:10.1016/j.biocel.2007.07.005

Cited by 148 publications

(105 citation statements)

References 20 publications

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“…These results demonstrated that the HS27 cells were killed as a result of the presence of the C. difficile toxin. In contrast, cholera toxin only provokes loss of water and electrolytes in epithelial cells, disrupting both cell attachment and cell-cell contact, while it does not cause cell death (46). At the concentration of 0.11 ng/ml, the nCI returned to 0.8 by approximately 11 h after treatment and continued increasing slowly (data not shown).…”

Section: Discussionmentioning

confidence: 92%

Quantitative Detection of Vibrio cholera Toxin by Real-Time and Dynamic Cytotoxicity Monitoring

et al. 2013

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eWe report here the quantitative detection of Vibrio cholerae toxin (CT) in isolates and stool specimens by dynamic monitoring of the full course of CT-mediated cytotoxicity in a real-time cell analysis (RTCA) system. Four cell lines, including Y-1 mouse adrenal tumor cells, Chinese hamster ovary (CHO) cells, small intestine epithelial (FHs74Int) cells, and mouse adrenal gland (PC12-Adh) cells, were evaluated for their suitability for CT-induced cytotoxicity testing. Among them, the Y-1 line was demonstrated to be the most sensitive for CT-mediated cytotoxicity, with limits of detection of 7.0 pg/ml for purified CT and 0.11 ng/ml for spiked CT in pooled negative stool specimens. No CT-mediated cytotoxicity was observed for nontoxigenic V. cholerae, non-V. cholerae species, or non-V. cholerae enterotoxins. The CT-RTCA assay was further validated with 100 stool specimens consecutively collected from patients with diarrhea and 200 V. cholerae isolates recovered from patients and the environment, in comparison to a reference using three detection methods. The CT-RTCA assay had sensitivities and specificities of 97.5% and 100.0%, respectively, for V. cholerae isolates and 90.0% and 97.2% for stool specimens. For stool specimens spiked with CT concentrations ranging from 3.5 pg/ml to 1.8 ng/ml, the inoculation-to-detection time was 1.12 ؎ 0.38 h, and the values were inversely correlated with CT concentrations ( ‫؍‬ ؊1; P ‫؍‬ 0.01). The results indicate that the CT-RTCA assay with the Y-1 cell line provides a rapid and sensitive tool for the quantitative detection of CT activities in clinical specimens. Vibrio cholerae is a Gram-negative, comma-shaped, bacterial pathogen causing cholera, an acute secretory diarrheal disease. Epidemic cholera is common in developing countries and affects about 100,000 people annually (1). Cholera toxin (CT) is a major virulence determinant of V. cholerae, leading to rapidly progressing dehydration, shock, metabolic acidosis, and even death within hours without adequate and appropriate therapy (2). CT is a key biomarker of V. cholerae that is used for forecasting and assessing epidemic disease, monitoring and controlling cholera outbreaks, preventing epidemics, and guiding medical personnel in providing timely treatment of patients. There has been urgent demand for the development of novel sensitive assays for the detection and identification of CT proteins.Conventional biochemical and immunological methods for CT detection and identification can be completed only after V. cholerae is isolated. The bacterial isolation and subsequent CT detection and identification are laborious and usually require several days, resulting in significant delays in patient care and disease control (3, 4). In addition, classic CT determinations require the use of either animal methods (5, 6) or tissue culture methods (7,8), which are also time-consuming and are subjective in the interpretation of results. Efforts have been made recently to develop more-sensitive methods, including enzyme-linked immunosorbent...

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Section: Discussionmentioning

confidence: 92%

Quantitative Detection of Vibrio cholera Toxin by Real-Time and Dynamic Cytotoxicity Monitoring

et al. 2013

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“…[1] For example, cholera is caused by an AB 5 protein toxin that has a single toxic Asubunit associated with five nontoxic B-subunits (CTB), which constitute a pentameric receptor for the GM1 glycolipid found on the surface of intestinal epithelial cells. [2] Multivalent binding between CTB and up to five copies of its GM1 ligand facilitates the entry of the toxin into the cell by endocytosis.…”

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confidence: 99%

A Protein‐Based Pentavalent Inhibitor of the Cholera Toxin B‐Subunit

et al. 2014

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Protein toxins produced by bacteria are the cause of many life-threatening diarrheal diseases. Many of these toxins, including cholera toxin (CT), enter the cell by first binding to glycolipids in the cell membrane. Inhibiting these multivalent protein/carbohydrate interactions would prevent the toxin from entering cells and causing diarrhea. Here we demonstrate that the site-specific modification of a protein scaffold, which is perfectly matched in both size and valency to the target toxin, provides a convenient route to an effective multivalent inhibitor. The resulting pentavalent neoglycoprotein displays an inhibition potency (IC 50 ) of 104 pm for the CT B-subunit (CTB), which is the most potent pentavalent inhibitor for this target reported thus far. Complexation of the inhibitor and CTB resulted in a protein heterodimer. This inhibition strategy can potentially be applied to many multivalent receptors and also opens up new possibilities for protein assembly strategies.

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“…After the pentameric B subunit of CT binds the GM1 ganglioside receptor, CT enters the cell and its catalytic-A subunit ADP ribosylates and activates the heterotrimeric guanine nucleotide bindingprotein G s , which then stimulates cAMP production by adenylyl cyclase. In intestinal epithelial cells, cAMP induces chloride secretion, leading to the massive fluid loss that characterizes cholera (4). The toxicity of CT prevents its use as an adjuvant in humans, but understanding the mechanisms underlying its adjuvant activity may lead to development of nontoxic mucosal adjuvants for clinical use.…”

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confidence: 99%

Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax

Datta

Sabet²,

Nguyen³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

144

129

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Cholera toxin (CT) elicits a mucosal immune response in mice when used as a vaccine adjuvant. The mechanisms by which CT exerts its adjuvant effects are incompletely understood. We show that protection against inhalation anthrax by an irradiated spore vaccine depends on CT-mediated induction of IL-17-producing CD4 Th17 cells. Furthermore, IL-17 is involved in the induction of serum and mucosal antibody responses by CT. Th17 cells induced by CT have a unique cytokine profile compared with those induced by IL-6 and TGF-β, and their induction by CT requires cAMP-dependent secretion of IL-1β and β-calcitonin gene-related peptide by dendritic cells. These findings demonstrate that Th17 cells mediate mucosal adjuvant effects of CT and identify previously unexplored pathways involved in Th17 induction that could be targeted for development of unique mucosal adjuvants.IL-17 | dendritic cell | T cell | vaccine | cAMP

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Vibrio cholerae: Cholera toxin

Cited by 148 publications

References 20 publications

Quantitative Detection of Vibrio cholera Toxin by Real-Time and Dynamic Cytotoxicity Monitoring

Quantitative Detection of Vibrio cholera Toxin by Real-Time and Dynamic Cytotoxicity Monitoring

A Protein‐Based Pentavalent Inhibitor of the Cholera Toxin B‐Subunit

Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax

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