BACTERIAL PATHOGENIC FACTORS

Helicobacter pylori expresses a number of putative factors of pathogen icity which could account for the gastroduodenal lesions observed in i nfected patients. An important factor of pathogenicity is the vacuolat ing toxin A. Molecular studies have shown a mosaic organisation of the vacA gene signal sequence (s) and middle sequence (m) regions, with t ype s1/m1 being associated with the highest levels of vacuolating acti vity of the expressed vacuolating toxin A protein, Vacuolating toxin A protein is secreted as monomers of M(r) 95 000. In-vitro, they organi se into polymers of approximately M(r) 700 000 and only oligomers stim ulate the production of neutralising antibodies, suggesting that aggre gation 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. pylo ri strains also express a protein called cytotoxin-associated gene pro tein A, Cytotoxin-associated gene protein A-positive strains carry gen omic regions, called picA and picB, which seem to be responsible for t he increased inflammatory potential induced by these organisms, Patien ts with active gastritis, peptic ulceration, and pre-neoplastic or neo plastic mucosal lesions are mostly infected by vacuolating toxin- and cytotoxin-associated gene A-positive strains. Mucosa-associated lympho id tissue-associated gastric lymphomas are not associated with the cyt otoxin-associated gene protein A status of the infecting organisms. Th e presence of Lewis(x) blood group antigen on the lipopolysaccharide o f H. pylori may play an important role in bacterial attachment and the development of autoimmunity in the host. Other potential pathogenicit y factors of H. pylori include urease, neuraminidase, haemolysins, fla gella and heat-shock proteins, but the role of these bacterial substan ces has not yet been fully determined.