Current treatments for H. pyloriinfection generally rely on broad-spectrum antibiotics, but the bacterium is becoming resistant and treatment fails in about 30% of cases.

In the new study, biologists and physicists at the University of Oregon (UO) in the US reveal how a protein in H. pylori, the acid receptor TlpB, grabs a small molecule called urea that helps it to sense and navigate away from highly acidic environments.

They write about their findings in the 14 June online issue of the journal Structure.

An important feature of the study is that the researchers found TlpB has a small platform that protrudes from the bacterium cell, which they identified as a "PAS domain". A PAS domain is a part of a protein that senses signals. Normally it resides inside cells, but in the case of TlpB in H. pylori it sticks out of the cell, reaching outwards, and binds to urea, giving it the ability to sense the external environment.

The researchers say this is the first time that crystallography has been used to show that a bacterial chemoreceptor contains a PAS domain that is outside the cell.

Co-author James Remington is professor of physics and member of the UO Institute of Molecular Biology. He told the press:

"It is a beautiful structure, and this domain has never been seen before in this class of proteins."

He and his colleagues managed to manipulate the atomic structure of the protein and disrupt its ability to bind to urea, and showed urea was the key to helping H. pylori sense and avoid acid.

Co-author Karen Guillemin, professor of biology and also a member of UO's Institute of Molecular Biology, said when the receptor is not able to bind to urea, the bacterium gets "confused" and can't navigate away from high acid:

"We found that this urea binding is absolutely crucial for this protein to act as an acid sensor."

Guillemin explained they now have "significant new insights into how acid sensing works at the atomic level which is important for H. pylori's life in the stomach."

"The health implications are this: If we disrupt the binding of urea, we can confuse the bacteria and potentially block their ability to reach the stomach lining where they cause damage," she added.

Remington said so far they only have "snapshots along the way" of how H. pylori's signals work. He said more work is now needed to understand the underlying mechanisms. 

But, he said, the structure they have revealed, allows researchers see the location of about 3,000 individual atoms in the urea-binding protein domain.

H. pylori is a Gram-negative bacterium that was first identified in 1982 and shown to be linked with stomach ulcers and stomach cancer. 

While we know little about how it spreads, it is present in the stomachs of half of the people in the world, 80% of whom will have no symptoms. 

Grants from the National Institutes of Health and the National Science Foundation helped support some of the researchers on the study.

Written by Catharine Paddock PhD 

Copyright: Medical News Today