0213 - Peptic Ulcer as an Infectious Disease Flashcards
Describe the drugs used to treat H. Pylori infection and their mode(s) of action.
PPI with amoxicillin and clarithromycin (know modes of actions). Amoxicillin targets peptidoglycan synthesis and clarithormycin hits the ribosomes. Point is that you want 2 antibiotics with different actions.
What is an adhesin? What adhesins does H. Pylori use?
Adhesin - A bacterial virulence factor that coordinates binding of the organism to a host tissue.
H. Pylori uses BabA, and SabA, as well as AlpAB, HopZ, and Urease
What is an impedin? What impedins does H. Pylori use?
Impedin - A bacterial virulence factor that enables the organism to evade the host’s defence mechanisms.
H. Pylori uses VacA and urease.
What is an aggresin? What aggresins does H. Pylori use?
Aggresin - A bacterial virulence factor that directly damages the host.
H. Pylori uses CagA, as well as VacA and urease. Together, these disrupt the epithelial barrier, promoting inflammation, leukocyte recruitment and apoptosis, leading to mucosal ulceration.
What is a modulin? What modulins does H. Pylori use?
Modulin - A bacterial virulence factor that induces damage to the host indirectly.
H. Pylori uses CagA and HP-NAP.
Describe H. Pylori
Gram Negative, rod-shaped bacteria with Flagella. Undergoes extracellular replication. Is well adapted to an acidic environment because of urease, an enzyme that converts urea to ammonia. Urease allows H. Pylori to colonise without competition. This leads to chronic infection in around 50% of global population, 80% of whom are asymptomatic.
Describe the adhesins uses by H. Pylori.
BabA - binds on Lewis B blood group antigens on host cells.
SabA - Binds monosaccharide sialic acid, binding to neutrophils resulting in oxidative burst.
Alp AB, HopZ - knockout strains show reduced adherence.
Urease - binds to MHCII, may induce apoptosis.
How does CagA serve as an aggressin and modulin?
Once injected by Type IV secretion system, CagA is phosphorylated and signals reorganisation of cytoskeleton, induction of NF-KB and IL-8 production, and recruitment of epithelial adhesion molecules to the site of bacterial infection. The barriers break down and stomach acid causes further destruction.
Ultimately, pro-inflammatory, disrupt tight junctions, carcinogenic, and increase cell motility. Also induces pedestal formation, leading to apoptosis.
Why is urease a powerful adhesin, aggresin, and impedin?
Allows H. Pylori to overcome acid production by catalyzing urea to ammonia and CO2. Excretes NH3 around surface of cell, neutralising acid (impedin) and creating alkaline micro-environment and damaging epithelium (aggresin). Also acts as adhesin (binds to MHCII), can induce apoptosis, and is pro-inflammatory.
What is VacA? How is it utilised by H. Pylori?
Pore forming toxin secreted by H. Pylori. Aggresin - induces vacuole formation in cells and disrupts membrane trafficking (including increasing urea transport, more favourable to H. Pylori). Disrupts the mucus membrane, allowing further damage by H+.
Describe the immune response to H. Pylori
Consists of innate and adaptive responses
Inflammatory response - Many antigenic compounds released, notably HP-NAP, leading to inflammatory response rich in IL-8. This leads to significant inflammation in the area.
Adaptive response - B-cells have a local and systemic response (IgG and IgA). T-cells are suppressed and focus on Th1 response, promoting inflammation.
