An%20infectious%20bacterium:%20Helicobacter%20pylori - PowerPoint PPT Presentation

About This Presentation

Title:

An%20infectious%20bacterium:%20Helicobacter%20pylori

Description:

... infection by sending white cells, killer T cells, and other infection ... In 1994, the national institute of health published an opinion stating that most ... – PowerPoint PPT presentation

Number of Views:139

Avg rating:3.0/5.0

Slides: 12

Provided by: huis5

Category:

more less

Transcript and Presenter's Notes

Title: An%20infectious%20bacterium:%20Helicobacter%20pylori

1
An infectious bacterium Helicobacter pylori

Tony
10/07/2005

2
http//nobelprize.org/medicine/laureates/2005/inde
x.html
3
Helicobacter pylori

A spiral shaped, Gram-negative, microaerophilic,
and flagellated bacterium, living in the stomach
and duodenum
About 3 microns long with a diameter of about 0.5
micron
Causing up to 80 of peptic ulcers, more than
90 of duodenal ulcers, and some types of
gastritis (http//www.cdc.org)
Rediscovered in 1982 by the laureates and made
connection with stomach ulcers and gastritis

Helicobacter pylori (blue bars, curved, 2-4
microns) localized in the mucus on the mucosa
surface, at the intercellular lines. Photo
tangential section of the gastric mucosa
http//www.pathologyatlas.ro/Helicobacter20pylori
.html
4
Symptoms

The most common ulcer symptom is burning pain in
the epigastrium (the upper middle region of the
abdomen). The pain typically occurs when the
stomach is empty.
Less common symptoms include nausea, vomiting,
and loss of appetite.
Bleeding can also occur.
Recent studies have shown an association between
long-term infection and the development of
gastric cancer, which is the most common cancer
in China.

http//www.cdc.gov/ulcer/md.htm
5
Epidemiology

Approximately two-thirds of the world's
population is infected with H. pylori.
70 - 90 in developing countries
25 - 50 in developed countries
Over half the population is infected in early
childhood in China.
Most of those infected never have symptoms.
The bacteria are most likely spread from person
to person through fecal-oral or oral-oral routes.
Possible environmental reservoirs include
contaminated water sources.
The source of H.pylori is not yet known.

http//www.cdc.gov/ulcer/md.htm
6
Pathogenicity
Stomach acid

H.pylori lives in the mucus lining to escape from
the highly acidic gastric juice. (Its helical
shape facilitates its penetration of the mucus
layer.)
It can fight the acid by excreting an enzyme
called urease.
The immune system responds to the infection by
sending white cells, killer T cells, and other
infection fighting agents.
However, they cannot easily get through stomach
lining to reach the infection.
As the immune response grows, immune cells die
and release destructive compounds on the stomach
lining cells.
Within a few days, gastritis and perhaps
eventually a peptic ulcer results.

Gastric epithelium
http//www.helico.com/
7
Virulence factors

Adhesion
adhesin-receptor interaction between BabA (from
H.pylori) and Lewis b antigen, the blood group
antigen expressed by gastric epithelial cells
Colonization factors
Urease
ureAb genes encode two units of the enzyme
ureEFGH genes encode the accessory proteins
responsible for incorporating nickel in the
center of the enzyme
ureI encodes the protein responsible for
transport of urea
Phospholipase A B
Responsible for destruction of the protective
mucous zone
Loss of this protective barrier allows the
stomach acid and digestive enzymes to have direct
access to the gastric epithelium.
Toxins
Cytotoxin associated gene A (CagA)
Part of the cagPAI, a 40Kb DNA fragment containg
between 27 and 31 genes.
Injected into host cells and cause the
deregulation of cell growth
Vacuolating cytotoxin A gene (VacA)
The vacuolating cytotoxin can target several
cellular types gastric epithelial cells,
macrophages, neutrophils and mast cells, and
several cellular compartments
Secretion of VacA and injection of CagA to host
cells ultimately induce the release of
chemotactic cytokines, which recruit inflammatory
cells to the area.

H.Pylori has been divided into Type I and Type II
strains based upon the presense of CagA and the
secretion of VacA.
OMahony et al., Sci Prog. 2004
8
Treatment Prevention

Antibiotic
The currently accepted management for the
eradication of H.pylori is a proton pump
inhibitor combined with two antibiotics
clarithromycin and either amoxycillin or
metronidazole (used in place of amoxycillin in
those allergic to penicillin).
Vaccine
Vaccines are being tested in animals and humans.
It is very early days yet.
Inhibitors of adhesion (some vegetables plant
fruits)
Cranberry juice
Seaweed Cladosiphon fucoidan
Spice turmeric
Fruit of okra plant

9
Genome

Two sequenced genomes available
Strain 26695
Strain J99
Genome size 1.6M bp
1,667,867 for strain 26695
Number of genes 1600
1609 for strain 26695
In silico model of metabolic network
Constructed by Palssons group at UCSD
341 metabolic genes
476 internal reactions
78 exchange reactions
485 metabolites

10
The way to the prize

Gastroenterologists resisted Marshall Warrens
idea.
It was hard for them to accept that the disease
could be simple infection.
Drug companies that profited from the anti-ulcer
drug market were so actively resistant.
Bacteriologists were suspicious --- the stomach
had long been assumed to be too acidic to host
bacteria.
In frustration, Marshall did the cause-and-effect
experiment
He swallowed a solution containing the bacteria,
and came down with gastritis and ulcers. (He
later recovered without treatment.)
The critics has not been softened, because of his
youth, and the fact that Royal Perth hospital has
no strong academic reputation.
In 1991, the centers for disease control and
prevention declared a link between H.pylori and
gastric disease.
In 1994, the national institute of health
published an opinion stating that most recurrent
gastric ulcers were caused by H.pylori.
In 2005, Warren Marshall were awarded the nobel
prize.