Helicobacter pylori.pdf - Academic lab pages - School of Biosciences

Bug of the Month
25.11.10

Discovered in 1983 (Nobel prize awarded in 2005)
Gram negative, spiral shaped bacterium
Member of the gamma proteobacteria
Microaerophilic
Infects ~50% of the human population worldwide
One of the most common infections in man
More common in less affluent regions of the world

Lives in the human stomach and duodenum
Able to survive the acidic conditions of the stomach by living in the
mucus lining (this also confers protection against the immune
system) and by converting the host’s urea into bicarbonate and
ammonia using a urease enzyme
Extracellular infection
Tends to cluster around cell junctions to allow urea to
Diffuse and to allow them to get nutrients

Asymptomatic in many people
Can lay dormant for many years
Causes chronic, multi-stage infection:
Gastritis – can occur after weeks/months or after decades
Peptic ulcers - caused by inflammation of the stomach lining
Stomach cancer – usually presents after years/decades

Biopsy (endoscopy) –eg –urease test
Breath tests – isotopically labelled urea is swallowed - measure
labelled CO2 when its exhaled
Serology – take blood samples and do ELISA using specific
antibodies

Elimination from the stomach cures symptoms
Triple therapy developed 1 st – metronidazole, ampicillin and bismuth
salts
Double therapy came later (1990’s)-amoxycillin and omeprazole
Ethical issue: Do we treat asymptomatic people –may have benefits
in earlier in life (may stop other pathogens taking a hold by
modifying the host environment)

Flagella: used for motility – allows it to move through mucus. If you
knockout flagella, you get decreased virulence
Toxins : Vac A causes cytoplasmic vacuolation . Exact role is still
unclear (possible epithelial cell damage?)
LPS
Adhesins : e.g. HpaA and BabA – allows it to stick to the host cells
Urease – neutralises stomach acid (protection) and produces
ammonia (damage). Urease mutants have decreased virulence.
Cag pathogenicity island
CagA protein – type 4 secretion pathway virulence effector

Eppinger et al (2006)
Humans have been colonised by H.pylori for at least 60,000 years
Evolutionary scientists have used H.pylori to track out of Africa
migration
Neighbour-joining trees show that there is less diversity in European
strains than African strains.
The African strain is more closely related to the big-cat strain
H.acinonychis Sheeba than the European strain is ... Did big cats
catch H.pylori from eating humans???
Atherton and Blaser (2009)
Since the out of Africa migration, it has been a part of the natural
microflora of humans
Modifies the host immune system long term and affects acid
homeostastis
Now, H.pylori is decreasing in prevalence due to improved living
conditions
Other diseases have emerged instead: gastroesophageal reflux
disease, obesity, type 2 diabetes, allergies
Is this disappearance and emergence linked?

Helicobacter pylori has been a part of the human microflora
throughout our history
It can cause disease, particularly in later life and has a host of
virulence factors to help it do this
However, it can lay latent in hosts for decades without causing any
problems and may even confer health benefits ...
Nasty pathogen ... Or cute and cuddly bug?!?