Getting rid of the bacterium Helicobacter pylori, a leading cause of stomach infections and ulcers, is incredibly difficult. It survives 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.
But researchers say they’ve unlocked the secret to how the bacterium latches to stomach sugars.
“Although it’s still very early, the insight we’ve gained from this study is already very exciting news for patients,” says Naim Hage, a postdoctoral researcher at the University of Nottingham who worked on the project.
Using 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.”
Franco Falcone, principal investigator of the project, says the next few years of 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.
AstraZeneca R&D sponsored the research, which appears in the journal Science Advances.
Source: University of Nottingham