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Effect of W07-toxin on gut physiological response in mice
Shalmoli Bhattacharyya1, Sujata Ghosh, Jasleen Shant
1Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India. shalmoli@glide.net.in
Abstract:
A number of unknown secretogenic factor(s) from Vibrio cholerae have been implicated to play a role in inducing cholera-like symptoms observed in patients. The present study has been carried out on the novel W07-toxin (pI 5.2) from V. cholerae W07, an epidemic cholera strain devoid of the ctx gene. The toxin showed maximum binding to GM(1) and interacted with a 20 kDa glycoprotein present on the cell membrane of mice enterocytes in a GM(1) specific manner. The analysis of biochemical parameters in enterocytes triggered with this toxin revealed a significant increase in intracellular calcium concentration and a massive secretion of Cl(-). However, no absorption of Na(+) was observed under the same condition. This toxin also elevated the level of cyclic adenosine 3',5'-monophosphate (cAMP) as well as protein kinase A (PKA). Thus, the novel toxin, although distinct from cholera-toxin, showed some functional homology to it and may be one of the key players inducing electrolyte imbalance within intestinal cells in the cholera-like symptoms associated with V. cholerae W07.
Insights
A novel W07-toxin from Vibrio cholerae induces cholera-like symptoms by increasing chloride secretion and intracellular calcium in intestinal cells. This secretogenic factor, distinct from cholera toxin, disrupts electrolyte balance.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- Vibrio cholerae secretes factors causing cholera-like symptoms.
- The ctx gene is typically associated with cholera toxin production.
- An epidemic V. cholerae strain W07 lacks the ctx gene but causes similar symptoms.
Purpose of the Study:
- To investigate a novel toxin from V. cholerae W07.
- To characterize the mechanism of action of this new toxin.
- To understand its role in electrolyte imbalance and cholera-like symptoms.
Main Methods:
- Isolation and characterization of W07-toxin.
- Toxin binding assays with GM(1) and enterocyte membranes.
- Biochemical analysis of intracellular calcium, chloride, and sodium transport.
- Measurement of cyclic adenosine 3',5'-monophosphate (cAMP) and protein kinase A (PKA) levels.
Main Results:
- The novel W07-toxin binds to GM(1) and a 20 kDa glycoprotein on mouse enterocytes.
- Toxin exposure significantly increased intracellular calcium and chloride secretion.
- Sodium absorption was not affected.
- Elevated levels of cyclic adenosine 3',5'-monophosphate (cAMP) and protein kinase A (PKA) were observed.
Conclusions:
- The W07-toxin is a novel secretogenic factor from V. cholerae.
- It induces cholera-like symptoms through mechanisms involving increased intracellular calcium and chloride secretion.
- Despite functional similarities to cholera toxin, it is biochemically distinct.
- This toxin may be a key factor in electrolyte imbalance caused by V. cholerae W07.
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