Download Helicobacter pylori evolution and phenotypic diversification in a

Helicobacter pylori
evolution and phenotypic diversification
in a changing host
Sebastian Suerbaum & Christine Josenhans
Asolina Braun
11.01.2010
History
-
Barry Marshall & Robin Warren, 1982
colonizes the stomach
link to gastritis and ulcers
Marshall ingests H. pylori => gastritis
2005 Nobel prize
- „for their discovery of the bacterium H. pylori and its role in gastritis
and peptic ulcer disease”
Clinics
• colonizes 50% of the world‘s population
• infection during infancy via family members
5,5% of all
cancer cases
Success Strategy
• extreme genetic diversity
– mutagenesis
– recombination
• host interaction
– outstanding evation of immune system
– immune suppression
Diversity
• extraordinary genetic heterogeneity
• every infected individual harbors their own
strain(s)
• strains change during infection
• high recombination events (multilocus enzyme
electrophoresis data, homoplasy test)
Geographical Distribution
• data based on multilocus sequence typing
Diversification by Mutagenesis
• defect mismatch repair
• defect base excision repair
• long repetitive sequences =>
– frameshift
– altered expression if located inside regulators
– intragenomic deletions/rearrangements
Diversification by Recombination
• recombination of short DNA fragments
(~417 bp vs. 2-10 kbp)
• 50% exchange of genome in 40 years
• 1,111 conserved genes + ~400
• frequent gene exchange
• seldom gene loss/gain (1 in 650 events)
Host Interaction
• BabA and SabA
– adhesins
– bind Lewis b and sialyl-Lewis on epithelium
– phase-variable expression
– adaptation to niches, acid conditions, …
– geographical correlation with blood groups
Host Interaction
• vacuolating cytotoxin (Vac A)
– vacuolation, tissue damage
– inhibits proliferation of T cells
– inhibits antigen presentation by B cells
• LPS
– Lewis antigens (on O-antigen side chains)
– binding of H. pylori to DCs via DC-SIGN =>
TH1 response diminished, ↓IL6, ↑IL10 =>
immune suppression
– heterogenous expression
Host Interaction
• flagellar motility
– implications unknown
• cag PAI (a chromosome segment)
– type IV SS
– destruction of the basal membrane
– atrophic gastritis, peptic ulcers,
adenocarcinoma (Ishikawa et al., PNAS, 2005)
Outlook
• prevalence in Western countries declines
– due to less mixed infections?
– due to better hygiene, antibiotics, broccoli?
• vaccination (Cag A)
Summary
• high prevalence of 50%
• extreme genetic diversity
– defective mutation repair systems
– many repetitive regions prone to mutations
– many recombination events
• outstanding evation of immune system
–
–
–
–
BabA and SabA
Vac A
LPS
Cag PAI