Helicobacter II

Question 1

What are the colonization factors of H.Pylori?

Answer 1

Helical shape, motility, urease, Super-oxide dismutase, catalase

Question 2

How does the helical shape of H.Pylori aid in its colonization of the stomach?

Answer 2

The spiral shape allows it to ‘drill’ its way into the mucus lining of the stomach which is an easier environment for colonization

Question 3

How does the motility of H.Pylori aid in its colonization of the stomach?

Answer 3

Polar flagella allow movement
Mucinase disrupts oligomeric strucutre of mucin allowing bacteria to penetrate
pH gradient in the stomach can be used for stomach spatial orientation
Non-motile models can not infect animal models
Motility and spatial orietnation are essential for H.Pylori to maintain its position

Question 4

Does H.Pylori live in the the stomach lumen?

Answer 4

No this environment is too acidic and H.Pylori will not survive there for long periods of time
Instead it occupies a niche very close to the tissue surface which is close to neutral pH

Question 5

How does urease aid in gastric colonization of H.Pylori?

Answer 5

It is essential for its survival at low pH as ti can neutralise acid by converting urea to CO2 and basic ammonia
It is highly important to the bacteria as it makes up 5% of total protein
It may also reduce viscosity of the mucus

Question 6

What is unique about the urease used by H.pylori?

Answer 6

Contains the Urease I gene which codes for a pore which can open and close in response to pH allowing some control over when urease operates

Question 7

How does superoxide dismutase and catalase aid in H.Pylori colonisation?

Answer 7

Aerobic respiration and the actions of innate immune cells can produce reactive oxygen species which can stress the bacteria
Superoxide dismutase breaks down super oxide while catalase breaks down peroxide to harmless water and oxygen

Question 8

What are the features of the catalase enzyme produced by H.Pylori?

Answer 8

It is very stable, thermostable, active in very high concentrations of peroxide
Active across a broad pH range
abundant almost being 1% of total cell content

Question 9

What are the immune evasion factors of H.Pylori?

Answer 9

Heterogeneity, adhesions and its unique lipopolysaccharide and flagellin

Question 10

How does the unique lipopolysaccharide of H.Pylori aid in immune evasion?

Answer 10

It is very different to other gram negative bacteria and 1000 times less pyrogenic and mitogenic
500 times less toxic
stimulates lower quantities of pro-inflammatory cytokines IL-1 and TNF
Its lipid A has a unique acylation and phosphorylation pattern
express Lewis y, Lewis X and H type I blood group strucures

Question 11

How does the unique flagellin of H.Pylori aid in immune evasion?

Answer 11

Its flagella is not as immunogenic not triggering toll-like receptor 5 and being 1000 times less potent than salmonella

Question 12

How does heterogeneity of H.Pylori come about?

Answer 12

This is due to a lack of mismatch DNA repair, repititve DNA allowing intragenomic recombination to change phenotype and its natural competence for DNA uptake

Question 13

How does the heterogeneity of H.Pylori act as an immune evasion factor?

Answer 13

Conserved genes are 92-99% identical between strains but some genes have much lower homology
It is not uncommon to be infected with more than one distinct strain
this enables h.pylori to rapidly adapt to the changing conditions of the host stomach and to new host stomachs

Question 14

What are the virulence factors of H.Pylori?

Answer 14

Adhesions, BabA/SabA, VacA, cag PAI

Question 15

How do adhesions on H.Pylori act as a virulence factor?

Answer 15

It enables the bacteria to resist removal by the host and close interaction with gastric epithelium for effective delivery of cytotoxins

Question 16

What are the features of H.Pylori’s adhesions?

Answer 16

4% of its genome codes for adhesions resulting in redundancy so none of the adhesions are in and of themselves essential also allows for variability between strains

Question 17

How are BabA and SabA virulence factors for H.Pylori?

Answer 17

During colonization H.Pylori expresses BabA which is an adhesion for gastric epithelial cells expressing Lewisb Blood group antigen
During chronic infection SabA is expressed which is an adhesion that binds to sialic acid which results in inflammed gastric epithelium and is associated wit hthe development of gastric cancer

Question 18

How is VacA a virulence factor of H.Pylori?

Answer 18

Vacuolating cytotoxin A is unique to H.Pylori and is a multifunctional toxin expressed by all H.Pylori strains though only half of them express a functional version
An active from of VacA is associated with an increased severity of disease

Question 19

How is cag PAI a virulence factor in H.Pylori?

Answer 19

cag PAI is associated with increased transmission and stimulates pro-inflammatory cytokines
Noted as the thing which commonly shifts H.Pylori from a commensal to a pathogen and is strongly associated with the development of gastric cancer

Question 20

What does PAI stand for?

Answer 20

PAI is a pathogenicity island which is characterised by different nucelotide composition to bacterial genome and is flanked by transposable elements, typically acquired by horizontal transfer

Question 21

What is cag PAI?

Answer 21

cytotoxin-associated Gene A, 40kb chromosomal PAI with 30 genes codes for an immuno-dominant protein

Question 22

How does cag PAI effect the host?

Answer 22

Codes for type 4 secretion system allows the toxin to enter the host cell including cytotoxin-associated gene A immunodominant protein as well as peptidoglycan
cagA interferes with a kinase signalling of a cell to induce morphological changes and cellular proliferation
Peptidoglycan can induce inflammatory responses

Question 23

What are the alternative approaches for dealing with H.Pylori infection?

Answer 23

There is suggestion of development of a vaccine, these work well in animal models however unfortunately do not work in humans as our tolerance for mucusal vaccines is low