Fighting back against stomach bacterium Helicobacter pylori

Posted Jan 1, 2017 by Tim Sandle
The bacterium Helicobacter pylori is linked with the formation of ulcers; there is also growing evidence with its connection to stomach cancer. In order to tackle the bacterium scientists have used neutrons to block the bacterium's metabolism.
H. pylori is a helix-shaped (classified as a curved rod  not spirochaete) Gram-negative bacterium ab...
H. pylori is a helix-shaped (classified as a curved rod, not spirochaete) Gram-negative bacterium about 3 μm long with a diameter of about 0.5 μm.
Institute for Systems Biology
The enzyme-attack is based on a study carried out by Professor Donald R. Ronning, who works at the University of Toledo, U.S. This is based on deploying neutrons to unlock a key enzyme in the bacterium's metabolism.
Helicobacter pylori is a microaerophilic bacterium found in the stomach of humans, especially those with chronic gastritis and gastric ulcers. The organism has been linked to the development of duodenal ulcers and stomach cancer. The vast majority (over 80 percent) of people infected with the bacterium are asymptomatic, and it is estimated that one in two people have the bacterium in their upper gastrointestinal tract.
The main therapy used to combat the bacterium consists of a combination of two antibiotics and a proton pump inhibitor. This procedure is, however, only successful in 70 percent of cases. Moreover, the level of resistance with the organism to the treatments is developing. This means a new approach is required.
This new approach is enzymatic. H. pylori uses a special enzyme to synthesize vitamin K2. As a result, this enzyme, 5'-methylthioadenosine nucleosidase (MTAN), provides an entry point for the formation of a new medication to act specifically against H. pylori. Specificity is important because medics would not want to harm other, often beneficial bacteria, that reside in the gut.
To determine the best point of attack, the research group used x-ray radiation to construct a structural analysis of the organism. At the molecular level this was based on neutrons.
Variations of the enzyme were next explored using a device called a BIODIFF diffractometer; this complex device allowed detailed measurements of the enzyme's mode of action to be formed. This revealed the binding sites for the enzyme, paving the way for a potential treatment.
It is hoped the new process can one day lead to a medication designed to combat the bacterium. The research is published in the journal PNAS, with the paper titled “Neutron structures of the Helicobacter pylori5′-methylthioadenosine nucleosidase highlight proton sharing and protonation states.”