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