Helicobacter pylori

Question 1

H.pylori is a ___ shaped ___ bacterium and is highly ____ through presence of ____

Answer 1

cork-shaped
Gram-negative
motile
flagella

Question 2

What environment does Helicobacter species utilise

Answer 2

Nitrogen rich environment - all urease positive

Question 3

How come H.pylori is microaerophilic

Answer 3

Does not tolerate high oxygen but does require at least 2% oxygen (to grow)

Question 4

H.pylori virulence factors

Answer 4

Genetically diverse (each infected person has a genetically unique strain)
Essential genes encode factors required for colonisation
- urease
- flagella for motility
- evading host immune system
Vac A + cag PAI (cag pathogenicity island)
Adhesin
oipA (outer membrane protein)

Question 5

H.pylori colonises the ___

Answer 5

Stomach

Question 6

Mode of action of Amoxicillin

Answer 6

Bacteriolytic, moderate spectrum against gram-positive = gram-negative
Inhibit transpeptidase enzyme by mimicking D-alanyl-D-alanine
Destabilises cell causing cell wall to be leaky + burst
Better absorbed orally

Question 7

Treatment regimen for eradicating H.pylori

Answer 7

Acid inhibition (PPI) + antibacterial treatment (antibiotic)
one week TRIPLE THERAPY
- PPI
- Clarithromycin
- Amoxicillin/Metronidazole (metronidazole if patient is sensitive to amoxicillin)

Question 8

If treatment is not effective, it indicates…

Answer 8

Bacterial resistance / poor compliance

resistance to amoxicillin is rare but to clarithromycin + metronidazole, it is common

Question 9

Mode of action of Clarithromycin

Answer 9

Erythromycin derivative with greater activity
Acid-stable so it can withstand stomach acids
Readily absorbed into tissues + phagocytes
High conc in phagocytes means it actively gets transported to site of infection
Macrolides inhibit protein synthesis by binding to 50s ribosomal subunit
Block translocation by preventing movement of peptidyl tRNA from A to P site

Question 10

Mode of action of Metronidazole

Answer 10

Metronidazole is a nitroimidazole
Broad-spectrum against anaerobic bacteria, protozoa + helminths
Prodrug - becomes active after reduction of nitro group in low redox environments
Reduction is non-enzymatic by reacting with ferredoxin
Metabolites are unstable + react with DNA causing irreversible damage

Question 11

Benefits of H.pylori infection

Answer 11

MAPPO
Metabolism - H.pylori suppresses ghrelin ( hormone which regulates body weight) impacting metabolic process in host
Asthma + allergies - reduced incidence of cagA+ H.pylori strains is associated with increased incidence of asthma + allergic disorders; cagA+ H.pylori with immune modulatory effect
Protection against infectious disease - through secretion of antimicrobial peptides; activating immune system, or competition
Personalised medicine
Oesophageal disorders - H.pylori colonisation reduces acid secretion, so if patient experiences reflux the reduced acid environment protects oesophageal epithelium from damage

Question 12

___ infection with H.pylori induces a ___ immune response

Answer 12

Natural

Humoral

Question 13

H.pylori inhibit ___ + ___; evading immune response + maintaining ___

Answer 13

T cell activation
Proliferation
persistent colonisation

Question 14

Trialled vaccine candidates

Answer 14

Recombinant Urease
Inactivate whole cells adjuvant
Combination of purified antigens
Live vector to urease

Question 15

Methods to diagnose H.pylori

Answer 15

Urea breath test
Stool antigen test
Blood test
CLO test

Question 16

Urea breath test

Answer 16

Patient fasts for 6 hours
Patient takes radioactively labelled urea
Metabolised H.pylori urease
Breath is analysed for radiolabelled CO2

Question 17

Stool antigen test

Answer 17

Used in children
Pea - sized stool sample taken
H.pylori antigens detected by ELISA - based method

Question 18

Blood test

Answer 18

Blood is tested for antibodies to H.pylori antigens

Common

Question 19

Biopsy (CLO test)

Answer 19

Mucosal tissue is taken at endoscopy + placed into a medium containing urea + pH indicator
Hydrolysis of urea to ammonia raises pH changing colour of indicator

Question 20

Bacterial adhesins

Answer 20

Binds H.pylori to gastric epithelial cells (includes BabA/SabA
BabA/SabA is linked with bacterial density + disease-risk

Question 21

VacA protein

Answer 21

Insertion of VacA proteins forms Anion-selective channels causing cells to be leaky.
Causes mitochondrial damage, apoptosis, epithelial cell breakdown, inhibits T-cell proliferation

Question 22

cag Pathogenicity Island

Answer 22

Encodes cagA - proteins that assemble into type IV (4) secretion apparatus
Type IV secretion injects cagA into gastric epithelial cells to cause inflammation

Question 23

Implications of H.pylori

Answer 23

Acute + chronic gastritis
Gastric + duodenal ulcers
Gastric atrophy
Gastric cancer

Question 24

Colonisation factors

Answer 24

Motility 
Environmental sensing
Chemotaxis
Iron acquisition
Acid resistance