Thwarting Helicobacter pylori infection

A pathogen found in around half the global population, Helicobacter pylori has been linked to the development of gastric diseases including gastritis, peptic ulcers and gastric cancer. Professor Thomas Bor?©n outlines the potential significance of research into its bacterial attachment mechanisms.

The Helicobacter pylori is one of the world’s most common infections, present in some 30 per cent of the population of Western Europe, while the worldwide prevalence is estimated to be even higher, at around 50 per cent. With the presence of the Helicobacter closely linked to the development of a number of conditions, ranging from gastritis to peptic (duodenal and gastric) ulcers right through to more severe diseases like gastric cancer, these are statistics which graphically illustrate the importance of continued research into the pathogen, such as that being undertaken by Professor Thomas Borén’s research group at Sweden’s University of Umeå.

“We started out by trying to identify those components – proteins – made by the Helicobacter that could be associated with the development of disease. This means proteins found among disease-associated Helicobacter strains. Our research has focused on the attachment process, because Helicobacter seems to be pretty efficient at attaching to the gastric mucosa – the stomach lining,” he explains.

Based at the University’s department of Medical Biochemistry and Biophysics, Borén’s group has been pursuing fundamental research into the structure and individual components of the Helicobacter. “After identifying the proteins in the pathogen we aim to then use them as key components in the creation of a vaccine against those diseases associated with the Helicobacter pathogen,” he continues. “We want to identify those components in Helicobacter which are associated with bacterial attachment, and that try to attach themselves to the gastric mucosa. We hope that the use of these stomach proteins as vaccine components will stimulate the body to produce an immune response of antibodies and cells that, in turn, will prevent the Helicobacter from attaching to the gastric mucosa; our goal is to eradicate infections that way.”

Around 1 per cent of infected people will go on to develop gastric cancer – about 1 million new cases each year world-wide – and with the condition known to be the world’s second most fatal cancer, inaction will have severe long-term consequences. This is increasingly widely recognised, particularly in countries like Japan and China which suffer from a high incidence of Helicobacter-related conditions, and although the link with gastric diseases was only established in the late ’80s, recent research advances have led to a real shift in therapeutics. “It’s now possible to treat peptic ulcers: when they appear you can treat them with antibiotics. That way you eradicate the Helicobacter infection and reverse the process. This allows the patient to heal their wounds; the net result is that with antibiotic treatment you can treat the patient without having to go into surgery. Surgeons used to have to remove a large part of a patient’s stomach just to get rid of ulcers,” explains Borén. The problem is that gastric cancer is currently incurable, and an enormous amount of antibiotics would be needed to treat the huge number of people who are Helicobacter infected. Worse still, the Helicobacter – as well as many other pathogens – would develop a resistance to the antibiotics. The group’s research currently focuses on the way in which the protein attaches itself to the stomach lining. Helicobacter typically inhabits various areas of the stomach and duodenum, and with our immune system seemingly unable to get rid of the infection by itself, Borén says it needs to be stimulated by external means.

“We need a vaccine to enhance the immune response to the Helicobacter, and to help the immune system identify the most crucial components of the pathogen – almost like a back-up to the bacteria – so that the immune system will gain some advantage, and really aim for the most important parts of the Helicobacter,” he explains. “When you culture it you need to include almost all of the available nutrients, whereas by comparison you can culture the E. coli bacteria in the bottle of a phosphate buffer. However, Helicobacter requires a lot of other nutrients – like amino-acids – during its development. We think that if we can interfere with that development process – by antibodies raised by the vaccine that could block it from attaching to the stomach lining – then we could possibly starve the infection of the nutrients it needs. In that way we could attenuate and eradicate the infection; that’s why we have focused on these attachment proteins.

“When I started this project we first identified those carbohydrate structures which Helicobacter binds to. These carbohydrates are very interesting, as they turn out to be the same carbohydrates which define the ABO blood group you belong to. These carbohydrates are present in not just the red blood cells in circulation, but are also expressed and presented on all the cells in the gastric intestinal lining. The ABO blood group can be found all the way from the oral cavity downwards on the epithelial cells, and Helicobacter attaches very firmly to these carbohydrates.”

The end result of this process can be severe, with the Helicobacter rapidly infecting areas of the stomach lining and causing not only chronic inflammation, but also often gastric disease. Currently there are no clear markers as to the likely severity of the infection, and how it will affect individual cases; nevertheless, Borén’s research into the structure and components of the Helicobacter still holds broad relevance. “The Helicobacter probably needs to attach itself to the gastric mucosa to gain nutrients, while this process is also necessary if it is to transfer virulence properties, like toxins and effector molecules to the host cells. So attachment is important to the development of infectious diseases,” he says. This kind of basic research is enormously important to the work of HeliCure, a University spin-off company dedicated to the development of vaccines against gastric cancer and ulcer disease, work which Borén is keen to pursue further. “I think it’s very important to continue to push vaccine development,” he comments, explaining that the research is very complicated, which has put-off big pharmaceutical companies. “When traditional means of vaccine development turns out to be insufficient then we need to come up with novel components; as such we are working to identify vaccine components that are more functional in terms of blocking infectious processes.”

For further information on the research, contact Professor Thomas Borén at Thomas.Boren@medchem.umu.se

Published: Wednesday, 2nd December 2009 by Patrick Truss

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