Helicobacter Pylori

Why is H. pylori an interesting bacteria? (4 reasons)

• 1. Survives in stomach (highly adapted to withstand acid)

• 2. Despite inducing chronic inflammation of the stomach lining (gastritis), it avoids being cleared by the human immune system and persists lifelong

• 3. Is extremely variable, high mutation rate, very polymorphic

• 4. it is a Class I carcinogen (causes ulcers and stomach cancer)

  • 6% of ALL cancer deaths worldwide are due to H. pylori

How is H. pylori adapted to survive in acidic conditions? (Flagella, spiral shape, chemotaxis, urease)

• Flagella - allows the bacterium to be highly mobile, enabling it to swim rapidly through the thick mucus lining of the stomach to reach the epithelial cell surface, which is a less acidic and more protected area

• Spiral shape - to facilitate its corkscrew-like penetration of the stomach's thick, viscous mucus layer, allowing it to reach and colonise the epithelial lining. This shape enhances motility within the mucus and helps the bacteria move toward the protective gastric pits (which are not as acidic) 

• Chemotaxis (ability to sense pH gradients) - H. pylori has sensory systems that detect chemical gradients, specifically sensing the difference between the acidic stomach lumen and the more neutral environment near the cells.

• Produces urease - digests urea into carbon dioxide and ammonia, making conditions more alkaline.

How does H. pylori evade the flow of food and mucus?

Adhesins (proteins on the surface of the bacterium that act like hooks) - They bind tightly to specific receptors on the surface of the stomach's epithelial cells, preventing the bacterium from being swept away by the constant flow of food and mucus.

Why does H. pylori produce catalase?

To protect itself from oxidative stress (H₂O₂ and HOCl) which are produced by the phagocytes during inflammation, hydrogen peroxide and hypochlorite are digested into water. This way the bacteria do not experience cellular damage and also results in a less acidic environment by dilution

How does H. pylori cause gastric ulcers in the stomach?

The persistent inflammation induced by the host's immune response, coupled with H. pylori's ability to neutralize these attacks with catalase, leads to chronic gastric mucosal damage which leads to gastric ulcers forming

What is CagA and T4SS?

The CagA protein itself is not a toxin until it gets inside a human cell. The bacterium uses a sophisticated molecular machine called a Type IV Secretion System (T4SS), which acts like a needle and syringe, to puncture the human cell's membrane and inject the CagA protein directly into it.

What it means: The genes needed to build the T4SS "syringe" and the CagA "ammunition" are all grouped on a specific segment of the bacterial DNA called the cag Pathogenicity Island (CagPAI). A "pathogenicity island" is a term for a cluster of genes that are acquired through evolution, which are responsible for making a bacterium virulent (disease-causing).

• Why it matters: This cluster allows all the necessary parts for this harmful function to be inherited and regulated together.

What does CagA actually do?

Cell Shape and Adhesion: It disrupts the cell's internal skeleton, leading to a characteristic "hummingbird phenotype" where the cell stretches abnormally. This weakens the protective stomach lining.

Cell Division and Death: It can send conflicting signals that lead to uncontrolled growth (a step towards cancer) and increase inflammation.

Inflammatory Response: It triggers the cell to release powerful inflammatory signals (cytokines), which leads to severe inflammation, tissue damage, and ulcers.

Why do some strains have CagPAI and some don’t?

• Not all H. pylori bacteria are identical. Some strains carry the entire CagPAI (they are Cag-positive), while others lack it entirely (they are Cag-negative).

• Why it matters: This genetic variation is the primary reason why infections can have different outcomes. You can be infected with a relatively benign strain or a more aggressive one

What is Vacuolating Cytotoxin A (VacA)? 

A type of toxin found in ALL H. pylori. Exists mainly as 2 strains s1/m2 strains, s2/m2 strains 

What does s1/m1 and s2/m2 mean?

• What it means: "Polymorphic" means the gene exists in many slightly different forms (alleles). The key variations occur in specific regions of the gene, most notably the signal region (s-region) and the middle region (m-region). Depending on the combination (e.g., type s1/m1 vs. s2/m2), the structure and function of the VacA toxin protein change.

• s1/m1 strains: Produce a highly active toxin. This form can efficiently form pores (holes) in human cells.

• s2/m2 strains: Produce a weak or inactive toxin. The protein is structurally different and much less effective at causing damage.

What are the 4 processes that VacA does?

Vacuolation: It creates large, acidic bubbles ("vacuoles") inside the host cell, disrupting its function and eventually killing it. This is where the toxin gets its name.

Pore Formation: It punches holes in the membranes of stomach cells and even immune cells. This disrupts the cell's environment, can trigger cell death, and weakens the stomach's protective lining.

Suppressing the Immune System: By damaging immune cells (T-cells), it helps the bacterium evade the host's immune response, allowing it to persist for decades.

Promoting Cancer Pathways: It can interfere with cell signaling in ways that may promote the development of cancer.