23. Vibrio cholrae causes diahorrea by
(1) Closing ion channels
(2) Constitutive expression of adenylate cyclase
(3) Closing absorption of water from gut epithelium
(4) Destroys cells of intestinal lining

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Introduction

Vibrio cholerae, the bacterium responsible for cholera, causes life-threatening diarrhea primarily by disrupting ion transport in the small intestine. Understanding the cellular and molecular mechanisms underlying this process is essential for grasping cholera pathogenesis and treatment approaches.

Mechanism of Diarrhea Induction by Vibrio cholerae

V. cholerae colonizes the small intestine and secretes cholera toxin (CT), which binds to intestinal epithelial cells. The toxin’s enzymatic A1 subunit catalyzes ADP-ribosylation of the Gs protein, locking it in an active state. This constitutively activates adenylate cyclase, elevating intracellular cyclic AMP (cAMP) levels.

Elevated cAMP leads to:

• Opening of CFTR chloride channels on the apical surface of enterocytes.

• Increased secretion of chloride ions into the intestinal lumen.

• Osmotic movement of water into the lumen following chloride.

• Inhibition of sodium and chloride absorption by microvilli.

Together, these effects cause massive fluid secretion into the intestinal lumen, producing the characteristic watery diarrhea of cholera.

Evaluating the Options

(1) Closing ion channels: Incorrect. CT opens chloride channels rather than closing them.

(2) Constitutive expression of adenylate cyclase: Incorrect wording; adenylate cyclase is constitutively activated, not expressed. The activation is due to toxin-modified G protein.

(3) Closing absorption of water from gut epithelium: Partially true but incomplete. The primary effect is increased chloride and water secretion rather than direct closure of absorption.

(4) Destroys cells of intestinal lining: False. V. cholerae is noninvasive and does not cause destruction of intestinal epithelial cells.

Correct Answer

Based on the mechanisms described in multiple studies and reviews, the most accurate answer is:

(2) Constitutive activation of adenylate cyclase

This process results in increased cAMP, leading to hypersecretion of ions and water, causing diarrhea.

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Summary

Vibrio cholerae causes diarrhea mainly by producing cholera toxin, which atypically activates adenylate cyclase continuously within intestinal epithelial cells. This leads to excessive chloride and water secretion into the gut lumen, overwhelming absorption and resulting in severe, watery diarrhea.

Understanding this mechanism guides effective treatment focusing on fluid replacement and supportive care.

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