Vibrio Cholerae: Characteristics and Virulence

• Vibrio cholerae is the bacterium responsible for cholera.
• It's caused by ingesting raw or undercooked seafood, water, and food.
• These bacteria are comma-shaped and highly motile, possessing flagella.
• Vibrio cholerae is divided into two groups based on cell wall antigens, namely the O1 group (causes epidemic) and the non-O1 group (nonpathogenic).
• It grows on most media including TCBS agar and alkaline peptone broth.
• Cholera is sensitive to stomach acid.
• People who use antacids or had a gastrectomy are more vulnerable.
• Virulence factors include enterotoxin secretion that causes ADP-ribosylation of membrane-bound G protein.
• This toxin activates adenylate cyclase, increases cAMP, and causes outflow of ions and water to the intestinal lumen, leading to diarrhea.
• Mucinase dissolves the protective glycoprotein coating on intestinal cells
• Symptoms include watery diarrhea in large volumes (rice-water stool), severe dehydration, cardiac and renal failure, acidosis, and hypokalemia.
• The mortality rate is 40% if untreated.
• Vibrio parahemolyticus is a major cause of diarrhea in Japan.
• Causes severe watery diarrhea, nausea, vomiting, abdominal cramps, and fever, typically self-limited to about 3 days.
• Vibrio vulnificus causes severe skin and soft tissue infections (cellulitis), septicemia in immunocompromised people, and hemorrhagic bullae on the skin.
• Diagnosis involves stool culture, oxidase-positive test, triple sugar iron test, and agglutination of polyvalent O1 or non-O1 antiserum, V. parahemolyticus grows in 8% NaCl solution.
• Treatment includes oral and IV water and electrolytes (with glucose for enhanced uptake), and tetracycline to shorten duration and reduce bacterial excretion.
• Vibrio parahemolyticus requires no specific treatment and can be prevented by proper refrigeration and cooking of seafood.
• Vibrio vulnificus can be treated with doxycycline.

Morphology and Classification

• Vibrio are comma-shaped, Gram-negative rods.
• They are highly motile via polar flagella.
• Vibrio cholerae O1 group causes epidemic disease.
• Non-O1 organisms either cause sporadic disease or are non-pathogenic.
• Vibrio cholerae O1 group is divided into three serotypes: Ogawa, Inaba, and Hikojima.
• Vibrio parahemolyticus and Vibrio vulnificus are marine organisms (halophilic).
• They thrive in warm salt water.

Growth and Identification

• Vibrio grow on common clinical lab media for stool and wound cultures like blood agar and MacConkey agar.
• Selective agars for Vibrios include thiosulfate citrate bile salts sucrose (TCBS) agar.
• Alkaline peptone broth can enrich Vibrio in mixed specimens.

Epidemiology

• Vibrio cholerae is transmitted by contaminated water and food.
• Vibrio parahemolyticus is transmitted by eating raw or improperly cooked seafood, especially oysters.
• Vibrio vulnificus is transmitted by eating raw shellfish or through shellfish handlers, especially oysters.
• Vibrio cholerae has two biotypes: classic and El Tor, and three serotypes: Ogawa, Inaba, and Hikojima.
• Natural disasters often precede cholera outbreaks.

Vibrio Cholerae Virulence Factors and Pathogenesis

• Pathogenesis depends on colonization in the small intestine and enterotoxin secretion.
• A large number of bacteria must be ingested for colonization due to sensitivity to stomach acid.
• People with low stomach acid (antacid users, gastrectomy patients) are more susceptible.
• Mucinase dissolves the intestinal cells' glycoprotein coating.
• This helps bacteria attach to the intestinal walls.
• After adhering, Vibrio cholerae multiplies and secretes cholera toxin (an enterotoxin).

Cholera Toxin Mechanism

• Cholera toxin has one A subunit and five B subunits.
• The B subunits bind to host cell receptors.
• The A subunit exhibits toxic activity, modifies a membrane associated protein that affects ion transport.
• Cholera toxin is similar to other bacterial AB toxins.
• The B subunits bind to ganglioside GM1 on intestinal cell membranes.
• Binding to GM1 triggers endocytosis.
• The toxin-containing vesicle is transported to the endoplasmic reticulum.
• The A1 peptide is released via a reduction reaction and transported into the cytoplasm, is an enzyme that modifies a G protein.
• The A1 peptide ADP-ribosylates a G protein, preventing it from inactivating adenylate cyclase.
• Elevated cAMP levels activates protein kinase A, which then activates ion transport channels like CFTR.
• CFTR exports chloride ions, and water follows to maintain osmolarity.
• This influx of fluid into the intestinal lumen results in diarrhea.
• Diarrhea aids in the bacterium's dissemination into the environment.

Clinical Manifestations

• Watery diarrhea in large volumes is typical (hallmark).
• Stool does not contain red or white blood cells.
• There is no abdominal pain initially; symptoms arise from severe dehydration.
• Fluid and electrolyte loss leads to cardiac and renal failure.
• Loss of bicarbonate and potassium in the stool causes acidosis and hypokalemia.
• Without treatment, mortality is around 40%.
• Vibrio parahemolyticus causes mild to severe watery diarrhea, nausea, vomiting, abdominal cramps, and fever, lasting about three days.
• Vibrio vulnificus causes severe skin and soft tissue infections (cellulitis).
• It can also cause rapidly fatal septicemia in immunocompromised patients.
• Hemorrhagic bullae in the skin often occur in Vibrio vulnificus infections.

Laboratory Diagnosis

• In epidemics, clinical judgment is often sufficient.
• For sporadic cases, culture of diarrheal stool is needed.
• Vibrio cholerae colonies appear colorless on MacConkey agar.
• The organism is oxidase-positive.
• On TSI agar, an acid slant and acid butt without gas or H2S are seen.
• Diagnosis can be confirmed by agglutination of the organism with polyvalent O1 or non-O1 antiserum.
• Vibrio parahemolyticus grows in 8% NaCl solution.

Treatment

• Treatment of cholera involves prompt replacement of water and electrolytes, orally or intravenously.
• Glucose is added to enhance water and electrolyte uptake.
• Tetracycline can shorten the duration of symptoms and reduce bacterial excretion.
• Doxycycline is recommended for Vibrio vulnificus infections.