Bacterial pathogenic factors

Helicobacter pylori expresses a number of putative factors of pathogenicity which could account for the gastroduodenal lesions observed in infected patients. An important factor of pathogenicity is the vacuolating toxin A. Molecular studies have shown a mosaic organisation of the vacA gene signal sequence (s) and middle sequence (m) regions, with type s1/m1 being associated with the highest levels of vacuolating activity of the expressed vacuolating toxin A protein. Vacuolating toxin A protein is secreted as monomers of M(r) 95,000. In-vitro, they organise into polymers of approximately M(r) 700,000 and only oligomers stimulate the production of neutralising antibodies, suggesting that aggregation is not casual. Monomers cleave in two fragments of M(r) 37,000 and 58,000. Both fragments penetrate cells in culture, but only the M(r) 58,000 subunit exerts a biological activity. Most cytotoxic H. pylori strains also express a protein called cytotoxin-associated gene protein A. Cytotoxin-associated gene protein A-positive strains carry genomic regions, called picA and picB, which seem to be responsible for the increased inflammatory potential induced by these organisms. Patients with active gastritis, peptic ulceration, and pre-neoplastic or neoplastic mucosal lesions are mostly infected by vacuolating toxin- and cytotoxin-associated gene A-positive strains. Mucosa-associated lymphoid tissue-associated gastric lymphomas are not associated with the cytotoxin-associated gene protein A status of the infecting organisms. The presence of Lewis(x) blood group antigen on the lipopolysaccharide of H. pylori may play an important role in bacterial attachment and the development of autoimmunity in the host. Other potential pathogenicity factors of H. pylori include urease, neuraminidase, haemolysins, flagella and heat-shock proteins, but the role of these bacterial substances has not yet been fully determined.