Transcript New Drug Targets for Cholera Toxin.

Cholera
By: Kelsey Duncan
http://fieldnotes.unicefusa.org/photos/
Cholera was discovered by Filippo Pacini.
Vibrio
Cholerae
Filippo Pacini, 1854
Robert Koch, 1883
Rosenberg, Charles E. (1987). The cholera years: the United States in 1832, 1849 and 1866.
Vibrio Cholerae is the causative agent.
http://en.wikipedia.org/wiki/Cholera
Reports of cholera probably barely scratch the surface.
WHO, http://www.phac-aspc.gc.ca/tmp-pmv/info/cholera-eng.php
Around the world,
an estimated 3-5
million cases and
over 100,000 deaths
occur each year.
WHO, 2012
Cholera can have different hosts!
Humans (intestines)
Marine Life (shellfish, oysters)
The main connection is water.
Ingested bacteria travel to the upper
small intestine, where they replicate.
Cholera expresses a toxin that leads to severe symptoms, and if
not treated, death.
A, B: cholera toxin
subunits
GM1: ganglioside
receptor
AC: adenylate cyclase
G: G protein
cAMP: cyclic AMP
CFTR: cystic fibrosis
transmembrane
conductance regulator
Trends Pharmacol Sci. 26, J. R. Thiagarajah and A. S. Verkman, New Drug Targets for Cholera Toxin.
Cholera toxin is
released from
bacteria in
infected
intestine
Toxin binds
through
interaction of
the B subunit of
the toxin with
the GM1
ganglioside
receptor.
Triggers
endocytosis of
toxin
Toxin undergoes
cleavage for A1
subunit to become
active enzyme
Inside cell: A1
fragment of toxin
subunit enters
cytosol and
activates G protein
Action
stimulates
adenlate
cyclase to
produce cAMP
High levels of
cAMP activate the
CFTR causing a
dramatic efflux of
ions and water
from infected
endothelial cells,
leading to watery
diarrhea
The main symptom is rapid and
major fluid loss.
Sudden onset and
large amounts of
watery diarrhea
Major Fluid Loss
Emed, http://diarrhea.emedtv.com/cholera/cholera-symptoms.html
The most effective treatment for cholera is
oral rehydration therapy.
Mayo Clinic, 2011
Two oral vaccines exist to
increase immunity.
Dukoral
Mutacol
Ryan, 2006, “Live Oral Cholera Vaccines”
To prevent cholera while traveling
follow these suggestions.
 Drink only water that you have
boiled
 Make sure all vegetables are
cooked
 Avoid undercooked or raw fish
or shellfish
 Avoid foods and beverages from
street vendors
 Do not bring perishable food
back to the United States
Emed, 2012,
http://diarrhea.emedtv.com/cholera/prevention-of-cholera-p2.html
Cholera outbreak officially announced in Haiti on October 22, 2010.
Paul Farmer, PIH, 2011
Many organizations, including
Partners in Health, are supplying aid.
Public health prevention in Haiti
and all developing countries is
crucial to eradicate cholera.
References

General information on vibrio cholera, cholera toxin, etc.


Cholera Toxin Pathway


WHO, 2008, http://www.who.int/topics/cholera/surveillance/en/index.html
Prevention


WHO/CDS/CSR/ISR/2000.1 WHO Report on Global Surveillance of Epidemic-prone
Infectious Diseaseshttp://www.who.int/csr/resources/publications/surveillance/en/cholera.pdf
Incidence Reports


http://diarrhea.emedtv.com/cholera/cholera-symptoms.html
Treatment


http://www.ebi.ac.uk/interpro/potm/2005_9/Page2.htm
Effects on Health


www.wikipedia.org
http://diarrhea.emedtv.com/cholera/prevention-of-cholera-p2.html
Epidemiology Report: Cholera in Haiti

Paul Farmer, Partners in Health, 2011, http://www.cdc.gov/haiticholera/haiti_cholera.htm