Motility and chemotaxis studies in Helicobacter pylori

H. pylori is one of the most common causes of chronic bacterial infection in man and its pathogenic role in the development of gastric and duodenal ulcers and gastric cancer is well documented. Chemotaxis is thought to be important in enabling H. pylori to reach the surface mucus layer in the stomach of infected subjects. Little is known about the mechanism of the chemotactic response or of its role played in the motility and virulence of H. pylori. Therefore the first step was to amplify and clone cheY and cheA homologues from H. pylori. Both CheY1 and CheAY had high identity to those found in other bacterial species. H. pylori N6 cheY1, cheAY, cheY, cheAY/Y1 and H. pylori SS1 cheY1 and cheAY isogenic mutants were constructed. The pattern of the chemotactic response was studied using swarm plates, capillary tube assays and computerised motility analysis. H. pylori CheAY seems likely to interact with the flagellar motor to bring about motor switching, whilst the CheY1 homologue acts to terminate the response. Mucin and urea were confirmed as chemoattractants and the results of the study were combined to produced a model of chemotaxis which differs from the E. coli paradigm in many respects. Finally the chemotaxis mutants were unable to colonise both the gnotobiotic piglet and mouse animal models confirming chemotaxis as a requirement for pathogenicity in H. pylori

Vaccination against type F botulinum toxin using attenuated Salmonella enterica var Typhimurium strains expressing the BoNT/F H(C) fragment.

The utility of the htrA, pagC and nirB promoters to direct the expression of the carboxy-terminal (H(C)) fragment of botulinum toxin F (FH(C)) in Salmonella enterica var Typhimurium has been evaluated. Only low levels of serum antibody were induced after immunisation, and some protection against botulinum toxin type F was demonstrated after oral immunisation of mice with two doses of any of these recombinant Salmonella. Immunisation with two doses of recombinant Salmonella expressing FH(C) from the htrA promoter gave the greatest protection, against up to 10,000 mouse lethal doses of botulinum toxin type F. These results demonstrate the feasibility of an orally delivered vaccine against botulinum toxin type F