Getting rid of the bacterium Helicobacter pylori, a leading cause of stomach infections and ulcers, is unbelievably hard. Through unique evolutionary adaptations, it can survive stomach acid by hiding in a layer of mucus.
Once inside the mucus, H. pylori 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 colonize with impunity.
Now, researchers say they’ve uncovered the secret to how the bacterium latches to stomach sugars. Says Naim Hage, a postdoctoral researcher at the University of Nottingham who worked on the project:
“Although it’s still very early, the insight we’ve gained from this study is already very exciting news for patients.”
Hydrogen Bond Network
With extremely powerful X-rays, Hage and colleagues studied the interactions between the H. pylori adhesion protein BabA and sugars at the atomic level. They found that right at its tip the protein has a specific groove that helps it to securely attach to sugars using a network of hydrogen bonds, the same kind of interactions that keep water molecules together.
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.
Scientists say the discovery is a promising step toward treating H. pylori infections, one of the most common bacterial infections worldwide and a leading cause of dyspepsia, peptic ulceration and gastric cancer.
“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,” says Hage. “If successful, this therapeutic strategy will also be extremely useful for treating H. pylori infections that are already resistant to antibiotics.”
Naim Hage, Tina Howard, Chris Phillips, Claire Brassington, Ross Overman, Judit Debreczeni, Paul Gellert, Snow Stolnik1, G. Sebastiaan Winkler and Franco H. Falcone Structural basis of Lewisb antigen binding by the Helicobacter pylori adhesin BabA Science Advances 14 Aug 2015: Vol. 1, no. 7, e1500315 DOI: 10.1126/sciadv.1500315
Illustration: University of Nottingham