A quick examination of the history of scientific discovery related to microbial pathogenesis confirms that scientists follow a predictable pattern of investigation. Typically, key virulence factors are identified and vaccines or therapies are designed to neutralise them. The characterisation of cholera toxin serves as an example of the potential benefits of being able to identify a single molecular entity that contributes to so much of humanity’s suffering. The understanding of the biological function of this molecule has yielded important insights into cell signalling, cytokine networks and mucosal immune regulation. Yamaoka and colleagues, in this issue (see page 442) have applied this time honoured approach in their studies of potential virulence factors associated with Helicobacter pylori. They show that isolates of H pylori bearing thecagA gene induce higher levels of cytokines and inflammation in the gastric mucosa than cagA− strains.

Studies to define virulence factors of H pyloriincluded the work of Leunk and colleagues who showed that H pylori produced a soluble factor that induced vacuolisation of epithelial cell lines.1 Shortly thereafter, the cytotoxin associated gene (cagA) and the vacuolating cytotoxin gene (vacA) were cloned and characterised. The link between virulence factors and disease was supported by Crabtree et al who astutely observed …