Researchers at Ludwig-Maximilians-Universität München (LMU) in Germany have discovered a weakness in the bacteria Helicobacter pyloriwhich can be used to develop new drugs.
H. pylori, a pathogen responsible for widespread diseases such as peptic ulcers and gastric cancer, has weak points, which can be exploited to create new drugs. This was discovered by a research group led by LMU biologists Rainer Haas and Wolfgang Fischer of the Max von Pettenkofer Institute of Hygiene and Medical Microbiology. The results have been published in the journal Cell Chemical Biology.
More than four billion people worldwide are infected with stomach bacteria, causing more than 800,000 cases of stomach cancer each year. Bacteria are becoming increasingly resistant to current drugs. This has led the World Health Organization (WHO) to classify it as a high priority pathogen for research and development of new antibiotics. New approaches and therapies are urgently needed to replace or complement existing treatment methods.
New studies have taken an important step in this direction.
“We were able to show that the bacteria are very sensitive to certain substances that inhibit cellular respiration,” said Haas.
Fighting helicobacter while protecting the gut microbiome
The researchers were able to identify several compounds from different groups of substances that paralyze the respiratory chain H. pylori, even in small concentrations. For other beneficial bacteria, including representatives of the normal gut microbiome, these substances pose no problem. These bacteria tolerate substances in larger quantities.
The study authors used a broad spectrum of biochemical and microbiological methods and molecular modeling techniques to find out why H. pylori react very sensitively to this group of substances. They identified the cause in a slightly modified structure of the so-called quinone binding pocket in respiratory complex I.
Researchers say this ‘Achilles heel’ offers great potential for the development of specially designed novel active agents that can be used as inhibitors of pathogens against H. pylori.
“Our results reveal a surprising weakness in the metabolism of these bacteria, which are otherwise well-adapted, to unusual environments,” said Fischer.
The research team at LMU was also able to identify possible mutations that make the bacteria less sensitive to the inhibitors. However, this mutation also weakens the metabolism of the pathogen. This means that less resistance is developed to the complex I inhibitor.
“Overall, our results are very promising,” Haas said.
“We were able to identify a whole group of inhibitors that did not show cross-resistance with current therapy. They are less susceptible to the development of resistance and have little impact on the gut microbiome.”
In addition to scientists at LMU, the German Center for Infection Research and researchers from the University of Ghent, the Max Planck Institute of Biophysics in Frankfurt, the Technical Universities of Munich, Helmholtz Munich and Helmholtz Braunschweig, Goethe University Frankfurt, and BASF Ludwigshafen all made significant advances contributing to the study.
In the fight against helicobacter, last year French pharmaceutical company Juvisé bought the worldwide commercial rights to Pylera from US biopharmaceutical company AbbVie. Pylera is a tri-therapy antimicrobial that helps treat H. pylori infection.