Identification of novel colonisation factors in Helicobacter pylori

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The discovery by Drs Marshall and Warren of the bacterium Helicobacter pylori, and its role in stomach disease, has proven to be one of the major break-throughs of the late 20th century. Indeed, several common ailments of the upper digestive tract that were once thought to be untreatable, or which could only be treated by radical surgery, are now managed through the use of antibiotics and acid-blocking substances. The efficacy of these treatments has, however, been affected by the increasing rates of H. pylori resistance to these antibiotics in the general community. Furthermore, the limited choice of antibiotics available for use in anti-H. pylori treatment regimens, and the side-effects associated with several of these compounds, suggest that there is a need to develop new therapies against this bacterial infection. This, however, will necessitate a greater understanding of the mechanisms by which H. pylori is able to colonise and survive in the mucus layer covering the stomach. To address this point, we have used a gene profiling technique to compare gene expression in H. pylori bacteria displaying high and low levels of colonisation in a mouse model. For this, mouse-colonising H. pylori bacteria were attenuated through extensive passaging on culture media in the laboratory. Five genes were identified as being poorly expressed in the attenuated bacteria. These genes are proposed to encode putative H. pylori colonisation factors. The aim of the project is to characterise these factors, and to determine the roles of two of these, which are involved in the production of vitamin B6, in the colonisation of the stomach. This work will contribute to a greater understanding of the factors involved in H. pylori colonisation of the stomach. Amongst the possible public health benefits of this work is the identification of molecular targets for the development of new therapies for the prevention and treatment of H. pylori infection.