New insights into H. Pylori unmask a 'molecular chameleon'

6 May 2016
​The bacterium ‘Helicobacter pylori’ is highly adapted to survival in the human stomach and is responsible for the majority of gastric ulcer and cancer cases worldwide. Scientists at the lab of Han Remaut (VIB/VUB) present new insights into BabA – a protein that plays a crucial role in H. pylori’s s survival strategy. We asked Kristof Moonens (postdoc) and Ayla Debraekeleer (PhD student) about their research that made the cover of Cell Host & Microbe.

First of all, what can you tell us about Helicobacter pylori?
Kristof: “This bacterium has been associated with mankind since ancient migrations and is still present in about half of the world population. It is responsible for the majority of gastric ulcer and cancer cases. Fighting it has become difficult, because of bacterial pathogens’ growing resistance to antibiotics. Nowadays, H. pylori eradication therapy requires sustained treatment with a cocktail of two or three different antibiotics. The quest for new treatment options or a vaccine is on.”

How does H. pylori manage to survive in noxious gastric juices?
Ayla: “An important survival strategy of the bacterium involves binding to the stomach mucosa, which keeps it out of the reach of gastric juices. H. pylori achieves this binding by adhering to blood group sugars found on gastric mucus and underlying cells. This interaction is made possible by the protein BabA. Our research provides new detailed structural and functional insights into that protein.”

What new information did you uncover?
Kristof: “This BabA protein proves to be a true ‘molecular chameleon’. It adapts its binding properties and preference for different ABO blood group sugars according to their prevalence in different human populations.

By determining the X-ray structures of different BabA proteins, we managed to establish a general framework for ABO blood group binding by the adhesin. Thomas Borén, a researcher from Umeå University in Sweden, had previously shown that ‘specialist’ H. pylori strains only bind to gastric tissue of blood group O individuals, whereas ‘generalist’ strains interact with all types of blood group individuals. Now we can show that a select network of residues in the protein steer the differences in binding preferences.”

How does this research provide clinical perspectives?
Ayla: “Our study also uncovered BabA’s Achilles heel. We have now shown that treatment with the redoxactive pharmaceutic N-acetylcysteine annihilates BabA function and, furthermore, that N-acetylcysteine lowers stomach inflammation in H. pylori-infected mice.

While the additive effect of N-acetylcysteine on antibiotic eradication therapies had already been reported, we have now found a molecular basis and explanation for this effect. This creates the basis for the rational design of novel, anti-adhesive drugs that will, hopefully, reduce bacterial attachment, stomach inflammation and hence lower the risk for overt disease development.”

Publication
Moonens et al., Cell Host Microbe. 2016

Research


The results inspired Ayla to draw the cartoon that features on the cover of Cell Host & Microbe.