Vibrio cholerae "Cholera"

What is the nickname for cholera?

Blue Death

Is Vibrio cholerae gram - or gram +?

Gram -

What shape is vibrio cholerae?

Curved rod

Is V. cholerae a faculative anaerobe?

Yes, it is a facultative anaerobe.

Why is V. Cholerae called the “Blue Death”?

Because it makes the skin turn blue-grey due to dehydration.

What effect of severe dehydration of cholera have on your bowl movements?

You have diarrhea. Shit 20 litres per day.

How soon after symptoms can you die from cholera?

Within 2-3hr of symptoms.

What is the V. cholerae reservoir?

humans, marine environments, shellfish

What is the transmission of V. cholerae?

Water contaminated with human feces, marine environment

What is NOT the transmission of v. cholerae? Why?

V. cholerae is not spread directly from person to person. Your body sheds the bugs 1-10 days after symptoms reside.

What is the disease caused by V. Cholerae?

Cholera

What are the main symptoms of V. cholerae?

• severe watery diarrhea

• intense thirst, abdominal cramps, blue-grey skin

• cardiac failure (low K+, K+ is needed for heart rhythm)

What are the general steps of pathogenesis for v. cholerae?

• bacteria is ingested

• bacteria colonizes small intestine

• CT (cholera toxin) is produced

• CT acts on mucosal cells, leading to diarrhea

  • rice water stool (flecks of mucosal cells)

  • dehydration, circulatory collapse, death

What are the virulence factors of v. cholerae?

Adherence toxins (Tcp, neuraminidase), CT: AB toxin, CT: ADPR Gs

What three virulence factors act as the first step to V. cholerae pathogenesis (Adherence)?

1. Tcp- toxin co-regulated pilus

2. Neuraminidase

3. CT

What does the Tcp- toxin co-regulated pilus do?

Binds to small intestinal mucosa and facilitates bug to bug attachment.

What does neuraminidase do and how does it help V. Cholerae?

It cleaves sialic acid from the intestinal mucosal surface. This "remodels" the cell surface to create more GM1 receptors, allowing more Cholera Toxin to bind and enter the cells.

How many toxins does CT have?

6 subunits: 1A, 5B (like PT)

What do the B subunits of v. cholerae do?

Attach to mucosal surface sugars

What does the A subunit of V. cholerae do?

It does ADP-Ribosylation of G proteins.

What does the ADPR of G proteins by CT lead to?

No inhibition of ACase by Gi, this leads to uncontrolled Cl- secretion into intestine, causing diarrhea.

What is the CT mechanism?

GPCR-Gs: G-protein-coupled receptor

• CT → ADPR-GS-GTP; rise in ACase and cAMP

• rise in cAMP activates PKA

• PKA phosphorylates CFTR uncontrollably

• rise in Cl- secretion; rise in Na+ and K+ ions

• efflux of fluid (water) into intestine

What is the treatment for cholera?

ORS: Oral Rehydration Solution

• glucose stimulates uptake of salts and water by mucosal cells

What is the vaccine for cholera?

VAXCHORA: a live, attenuated oral vaccine

• deletion of ctxA gene (no toxin)

• retain ctxB (Ab prevent bug binding)

What is the difference between Pertussis toxin and Cholera toxin in terms of ADPR?

CT ADPRs Gs while PT ADPRs Gi. When Gs is ADPR, Gi can’t inhibit it.