1. Sebastian Suerbaum & Christine Josenhans
Helicobacter pylori evolution and phenotypic diversification in a changing host
Sebastian Suerbaum & Christine Josenhans
Asolina Braun

2. 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”

3. Clinics colonizes 50% of the world‘s population
infection during infancy via family members
5,5% of all cancer cases

4. Success Strategy extreme genetic diversity host interaction
mutagenesis
recombination
host interaction
outstanding evation of immune system
immune suppression
thouthands in 1 nL
no higher incidence in immunocompromised

5. 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)

6. Geographical Distribution
data based on multilocus sequence typing
MLST set of housekeeping genes
housekeeping genes not under high selective pressure
none of modern strains derived from one ancestor
big migration waves can be traced

7. Diversification by Mutagenesis
defect mismatch repair
defect base excision repair
long repetitive sequences =>
frameshift
altered expression if located inside regulators
intragenomic deletions/rearrangements
mismatch repair during replication, methylated strand = ok BER alcylation, ROS, deaminated
repetitions in antimutator gene => regulation of mutation by mutation
last: cagA, amiA (peptidoglycan), fucosylation, LPS

8. Diversification by Recombination
recombination of short DNA fragments (~417 bp vs kbp)
50% exchange of genome in 40 years
1,111 conserved genes + ~400
frequent gene exchange
seldom gene loss/gain (1 in 650 events)
still some debate about numbers

9. 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
phase-variable => at any time some H.p. don‘t express it
BabA generalists vs BabA specialist (O AmerIndians)

10. Host Interaction vacuolating cytotoxin (Vac A) LPS
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

11. Host Interaction flagellar motility cag PAI (a chromosome segment)
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)
vaccine cagA

12. Outlook prevalence in Western countries declines vaccination (Cag A)
due to less mixed infections?
due to better hygiene, antibiotics, broccoli?
vaccination (Cag A)

13. 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

14. Thank you for your attention