H. pylori Virulence Factors: Toxins (CagA, VacA, DupA, OipA, IceA)

Abstract

Helicobacter pylori (H. pylori) specifically colonizes the human stomach. The majority of bacteria live in the mucus layer overlying gastric epithelial cells and only a small proportion of bacteria are found interacting with the epithelial cells. To succeed in the long-term colonization, H. pylori has developed a unique set of virulence factors, which allow survival in a harsh ecological niche. Clinical outcomes associated with H. pylori infections are largely mediated by a complex interaction between bacterial, host, and environmental factors. Over the past year, a variety of studies focusing on both host and bacterial factors have proceeded. Among the bacterial factors that contribute to the pathophysiology associated with H. pylori infections, it is remarkable that the cytotoxin-associated gene A (CagA) protein is delivered into gastric epithelial cells via bacterial type IV secretion system, leading to induction of diverse immune responses and gastroduodenal diseases. The vacuolating cytotoxin (VacA) is also one of the most important virulence factors and functions as an intracellular-acting protein exotoxin, in which one of the most important target sites for VacA is the mitochondrial inner membrane in the host. In addition, the outer membrane inflammatory protein (OipA), the induced by contact with epithelium (IceA), and duodenal ulcer promoting (dupA) gene have emerged as virulence factors, although the specific genes involved in virulence are still being determined. This chapter summarizes the results of the most relevant studies regarding H. pylori virulence factors such as CagA, VacA, OipA, IceA, and dupA gene and discusses their molecular mechanism for generating gastrointestinal diseases.