Helicobacter pylori Flashcards
H.pylori is a ___ shaped ___ bacterium and is highly ____ through presence of ____
cork-shaped
Gram-negative
motile
flagella
What environment does Helicobacter species utilise
Nitrogen rich environment - all urease positive
How come H.pylori is microaerophilic
Does not tolerate high oxygen but does require at least 2% oxygen (to grow)
H.pylori virulence factors
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)
H.pylori colonises the ___
Stomach
Mode of action of Amoxicillin
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
Treatment regimen for eradicating H.pylori
Acid inhibition (PPI) + antibacterial treatment (antibiotic)
one week TRIPLE THERAPY
- PPI
- Clarithromycin
- Amoxicillin/Metronidazole (metronidazole if patient is sensitive to amoxicillin)
If treatment is not effective, it indicates…
Bacterial resistance / poor compliance
resistance to amoxicillin is rare but to clarithromycin + metronidazole, it is common
Mode of action of Clarithromycin
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
Mode of action of Metronidazole
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
Benefits of H.pylori infection
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
___ infection with H.pylori induces a ___ immune response
Natural
Humoral
H.pylori inhibit ___ + ___; evading immune response + maintaining ___
T cell activation
Proliferation
persistent colonisation
Trialled vaccine candidates
Recombinant Urease
Inactivate whole cells adjuvant
Combination of purified antigens
Live vector to urease
Methods to diagnose H.pylori
Urea breath test
Stool antigen test
Blood test
CLO test
Urea breath test
Patient fasts for 6 hours
Patient takes radioactively labelled urea
Metabolised H.pylori urease
Breath is analysed for radiolabelled CO2
Stool antigen test
Used in children
Pea - sized stool sample taken
H.pylori antigens detected by ELISA - based method
Blood test
Blood is tested for antibodies to H.pylori antigens
Common
Biopsy (CLO test)
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
Bacterial adhesins
Binds H.pylori to gastric epithelial cells (includes BabA/SabA
BabA/SabA is linked with bacterial density + disease-risk
VacA protein
Insertion of VacA proteins forms Anion-selective channels causing cells to be leaky.
Causes mitochondrial damage, apoptosis, epithelial cell breakdown, inhibits T-cell proliferation
cag Pathogenicity Island
Encodes cagA - proteins that assemble into type IV (4) secretion apparatus
Type IV secretion injects cagA into gastric epithelial cells to cause inflammation
Implications of H.pylori
Acute + chronic gastritis
Gastric + duodenal ulcers
Gastric atrophy
Gastric cancer
Colonisation factors
Motility Environmental sensing Chemotaxis Iron acquisition Acid resistance
