Table 2.
Virulence factors closely associated with the carcinogenic mechanism of HP.
| Virulence factors | Mechanisms | Functions | |
|---|---|---|---|
| Pathogenic factors | CagA (36, 37) | • Transfection into cytoplasm by T4SS • Phosphorylation of tyrosine |
• Disrupts intercellular junctions • Facilitates inflammation • Causes cell proliferation • Promotes EMT |
| VacA (38, 39) | • Selective anion channel properties • Targets different organelles |
• Promotes HP colonization • Induces apoptosis and necrosis • Causes cell vacuolization • Enhances autophagy |
|
| NAP (40–43) | • Overactivation of ERK and p38-MAPK pathways • DNA-binding protein • Structurally similar to bacterial ferritin |
• Activates neutrophils, monocytes, and mast cells • Produces ROS • Promotes neutrophils’ adhesion to gastric epithelial cells • Promote the release of IL-8, IL-6, TNF-α, MIP-1α, MIP-1β, and β-hexosaminidase • Damages the gastric mucosa • Accelerates the process of chronic gastritis • Protects HP DNA from oxidative damage • Promotes the growth and colonization of HP |
|
| HtrA (44, 45) | • Serine proteases • Chaperones |
• Cleaves E-cadherin • Disrupts intercellular junctions • Disrupt the epithelial barrier • Enhances CagA translocation • Removes the wrong protein |
|
| gGT (46–48) | • Promotes biochemical reactions • Glutamine hydrolysis |
• Damages the gastric epithelium • Causes Glutathione consumption • Produces ROS • Causes cell cycle arrest • Induces apoptosis and necrosis • Induces immune tolerance • Up-regulates IL-8, caspase-3, caspase-9, and COX-2 • Enhances VacA-Dependent Vacuolation |
|
| Adhesion factors | BabA (49, 50) | Binds to Leb receptors on gastric epithelial cells | • Facilitates HP adhesion and colonization • Enhances CagA translocation • Activates inflammation |
| SabA (51) | Binds to the sialyl-Lex antigens | • Facilitates HP adhesion and colonization • Promotes neutrophil activation and infiltration • Induces oxidative damage • Causes inflammation |
|
| OipA (52–54) | Unknown | • Facilitates HP adhesion • Inhibits DC maturation • Induces apoptosis • Causes neutrophilic infiltration • Mediates CagA translocation • Increases IL-8 secretion • Decreases IL-10 expression |
|
| HopQ (55–57) | Binds to the CEACAM receptors | • Facilitates HP adhesion • Enhances CagA translocation • Promotes the release of IL-8 and MIP-1α • Inhibits immune cell activities • Protects tumor cells |
|
| HopZ (58, 59) | Unknown | • Facilitates HP adhesion • Causes infection • Inhibits gastric acid secretion |
CagA, Cytotoxin-Associated Gene A; VacA, Vesicular Cytotoxin A; NAP, Neutrophil-Activating Protein; HtrA, High Temperature Requirement A; gGT, γ-Glutamyl Transpeptidase; BabA, Blood Group Antigen-Binding Adhesin; SabA, Sialic Acid-Binding Adhesin; OipA, Outer Inflammatory Protein; Hop, Helicobacter pylori Outer Membrane Protein; T4SS, Type 4 Secretion System; EMT, Epithelial-Mesenchymal Transition; HP, Helicobacter pylori; ROS, Reactive Oxygen Species; DC, Dendritic cell.