Revealed: Helicobacter pylori's secret weapon

August 14, 2015, University of Nottingham
Helicobacter pylori
Histopathology of Helicobacter pylori infection in a gastric foveolar pit demonstrated in endoscopic gastric biopsy. Credit: Wikipedia.

Discovered in 1982, Helicobacter pylori (H. pylori) is a disease-causing bacterium that survives in our stomachs despite the harsh acidic conditions. It is estimated that one in two people have got it, though most won't ever experience any problems. Even so, it is considered one of the most common bacterial infections worldwide and a leading cause of dyspepsia, peptic ulceration and gastric cancer.

Through unique evolutionary adaptations, H. pylori is able to evade the antiseptic effect of our by hiding within the thick acid-resistant layer of mucus that coats the stomach wall. Once within the , the latches onto sugars naturally found on the stomach wall using its adhesion proteins. This attachment is so effective that the bacterium can resist attempts by the body to 'flush' it away, allowing the pathogen to colonise with impunity.

But the game could be up for H. pylori. Researchers in the School of Pharmacy, at The University of Nottingham and AstraZeneca R&D have identified the molecular mechanism that the bacterium's best-known adhesion protein uses to attach to stomach sugars. The research is published today, August 14 2015, in the prestigious scientific journal Science Advances.

Powerful x-rays reveal special 'groove'

Finding the molecular interactions that make this pathogen so successful in such a harsh environment has, until now, proved elusive.

Naim Hage, the postgraduate researcher who worked on this project as part of his doctoral thesis, said: "Although it's still very early, the insight we've gained from this study is already very exciting news for patients."

Using extremely powerful x-rays, the scientists were able to study the interactions between the H. pylori adhesion protein BabA and Lewisb sugars of the gastric mucosa at the atomic level. They found that, right at its tip, BabA possesses a specific groove that enables it to securely attach to Lewisb using a network of hydrogen bonds (the same kind of interactions that keep water molecules together).

Helicobacter pylori is a leading cause of peptic ulceration and gastric cancer worldwide. To achieve colonization of the stomach, this Gram-negative bacterium adheres to Lewisb antigens in the gastric mucosa using its outer membrane protein BabA. Movie shows the the structural basis of Lewisb antigen binding by BabA, as determined by x-ray crystallography. Credit: University of Nottingham / AstraZeneca R&D
First exciting step

The research team also found that this network is finely tuned - if a few of the hydrogen bonds are disrupted, the network doesn't function and binding can no longer occur. This insight into the required for adhesion is a promising lead for the development of new strategies for the treatment of H. pylori infections.

This study now forms the foundation for future research between The University of Nottingham and AstraZeneca R&D into "anti-adhesion strategies" that would work by clearing H. pylori out of the stomach through dislodging the bacterium off the using BabA:Lewisb inhibitors. Such novel strategies are needed to help treat H. pylori infections, which are globally gaining resistance to conventional antibiotic therapies.

Naim said: "Because BabA is unique to H. pylori, we can specifically target, and hopefully eradicate, this bacterium without affecting the other good bacteria in our normal flora. If successful, this therapeutic strategy will also be extremely useful for treating H. pylori infections that are already resistant to antibiotics."

More research to be done

The principal investigator behind the project, Dr Franco Falcone, said: "While this study answers long-standing questions about how H. pylori colonises the stomach, it represents the very first step in the development of novel therapies. The next few years of laboratory-based research will be crucial to determine if an anti-BabA adhesion approach is viable and can progress to clinical development. A similar approach is already showing promising results for the treatment of urinary tract infections in preclinical models. Looking forward, we are excited to continue working closely with AstraZeneca R&D who have provided a tremendous amount of support to achieve this discovery."

Explore further: Targeting the strain of bacteria that causes ulcers may help prevent stomach cancer

More information: Structural basis of Lewisb antigen binding by the Helicobacter pylori adhesin BabA, Science Advances, advances.sciencemag.org/content/1/7/e1500315

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Gigel
5 / 5 (1) Aug 14, 2015
This bacterium may be another good one that happens to live in a disturbed medium as a result of our diet, which gives it a higher population and thus leads to disease. Maybe the sugars in our diet feed it and that is what keeps Helicobacter dangerous. In that case a more sensible approach would be to try to control the bacterium.

From my experience, an acidic menu poor in sugars from time to time may control it. E.g. yogurt is acidic. Of course, those with ulcer or gastritis have to be careful and need medical advice on this. I learned to never try something possibly dangerous before going to sleep, in order to avoid having surprises when I cannot react. It is generally good to stick to foods that are known not to cause problems and never try something radically new on a sick stomach. Treatment has to be well tolerated; foods that cause distress can't be used as treatment. Also, simply avoiding foods rich in sugars may help.
scalefreenetwork
not rated yet Aug 16, 2015
Describing Helicobacter pylori as 'a disease-causing bacterium' is overly-reductive, and ignores a growing understanding - championed by Martin Blaser and others - of the role H. pylori has potentially played in the healthy human stomach for tens of thousands of years.
The above comment (by Gigel) is correct to suggest that H. pylori might well be another good guy gone bad "as a result of our diet"!
While this new research into the molecular basis of adhesion is fascinating - we need to stop treating bacterial infections as a war - and instead direct our efforts towards mediating conditions of peace and coexistence.
Addressing our high sugar diets would be a good start.
wangyizhuss
not rated yet Aug 17, 2015
I imagine that the bacterium is one cause to affect the eating appetite.
jhnycmltly
not rated yet Aug 19, 2015
"Vegetable oil ingredient key to destroying gastric disease bacteria"
"LipoLLA is a lipid (fat) particle that contains linolenic acid. When LipoLLA encounters H. pylori, it fuses with the bacterial membrane. Then the particle's linolenic acid payload spills out, disrupting the membrane and killing the bacteria."

Vegetable oil kills it, so one might wonder what the incidence of h.pylori infection is in vegetarians versus omnivores?
"If the Helicobacter pylori bacterium is found in the stomach, the risk of stomach cancer for persons with a high intake of meat increases fivefold."

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