Abstract
Helicobacter pylori is a well-recognized pathogen that chronically infects more than 50 % of the world's population. H. pylori plays an important role in the development of peptic ulcers, gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue lymphoma (MALToma). The infection remains latent in the majority of infected patients, with only approximately 20 % of infected individuals developing severe disease. It is unclear what determines the outcome of an infection; however, it is thought to involve an interplay between the virulence of the infecting strain, host genetics and environmental factors. Experience with other bacterial pathogens suggests that H. pylori-specific factors may exist that influence the pathogenicity of H. pylori.
Many putative virulence genes of H. pylori have been reported to determine clinical outcome, and these are generally classified into three categories (Table 1). The first category contains strain-specific genes, which are present in only some H. pylori strains. Among this group, the best studied is the cag pathogenicity island (PAI), which encodes a bacterial type IV secretory apparatus (Censini et al., 1996). The cag PAI contains approximately 30 genes, including the cagA gene in the 3' end of the island, which injects CagA and possibly other bacterial proteins into host cells (Asahi et al., 2000; Backert et al., 2000; Odenbreit et al., 2000; Segal et al., 1999; Stein et al., 2000; Viala et al., 2004). Strains that possess the cag PAI/cagA are statistically more likely to be associated with peptic ulcer and gastric cancer than are strains lacking the PAI/cagA (Blaser et al., 1995; van Doorn et al., 1998). To date, the complete genomes of three H. pylori strains (26695, J99 and HPAG1) have been sequenced (Alm et al., 1999; Oh et al., 2006; Tomb et al., 1997). These are all cag PAI-positive strains; however, many other strain-specific genes lie outside of the cag PAI (Table 2) and nearly half of the strain-specific genes of H. pylori are located in the plasticity region. Genes in this region are also good candidates for H. pylori virulence factors, as described in detail in this review.