helicobacter pylori evolution and phenotypic diversification in a changing host asolina braun...
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Helicobacter pylori
evolution and phenotypic diversification in a changing host
Asolina Braun11.01.2010
Sebastian Suerbaum & Christine Josenhans
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