Researchers at Ludwig-Maximilians-Universität München (LMU) in Germany have discovered a weakness in the bacterium Helicobacter pylori, which could be exploited to develop new drugs.
H. pylori, a pathogen responsible for widespread illnesses such as gastric ulcers and stomach cancer, has a weak point, which could be exploited to create new drugs. This was discovered by a research group led by LMU biologists Rainer Haas and Wolfgang Fischer from the Max von Pettenkofer Institute of Hygiene and Medical Microbiology. Their results have been published in the journal Cell Chemical Biology.
More than four billion people worldwide are infected with the stomach bacterium, leading to more than 800,000 annual cases of stomach cancer. The bacterium is becoming increasingly resistant to current drugs. This has led the World Health Organization (WHO) classifying it as a pathogen with high priority for the research and development of new antibiotics. New approaches and therapeutics are urgently required to replace or complement established treatment methods.
The new study has taken an important step in this direction.
“We were able to demonstrate 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 various substance groups that incapacitate the respiratory chain of H. pylori, even in small concentrations. For other useful bacteria, including representatives of the normal gut microbiome, these substances are unproblematic. These bacteria tolerate larger amounts of the substances.
The authors of the study used a broad spectrum of biochemical and microbiological methods as well as molecular modeling techniques to discover why H. pylori reacts so sensitively to these substance groups. They identified the cause in a slightly modified structure of the so-called quinone binding pocket in respiratory complex I.
The researchers said this ‘Achilles heel’ offers great potential for the development of specifically tailored new active agents that could be used as pathogen blockers against H. pylori.
“Our results reveal a surprising weakness in the metabolism of these bacteria, which are well adapted otherwise, to their unusual environment,” Fischer said.
The research team at LMU was also able to identify possible mutations that would make the bacteria less sensitive to the inhibitors. However, these mutations also weaken the metabolism of the pathogens. This means that less resistance is formed to the complex I inhibitors.
“Overall, our results are very promising,” Haas said.
“We managed to identify a whole group of inhibitors that do not exhibit any cross-resistance with current therapeutics. They are less susceptible to the development of resistance and have a small impact on the gut microbiome.”
In addition to scientists at LMU, the German Center for Infection Research and researchers from Ghent University, the Max Planck Institute of Biophysics in Frankfurt, the Technical University of Munich, Helmholtz Munich and Helmholtz Braunschweig, Goethe University Frankfurt, and BASF Ludwigshafen all made significant contributions to the study.
In the fight against helicobacter, last year French pharmaceutical company Juvisé bought worldwide commercial rights to Pylera from U.S. biopharmaceutical company AbbVie. Pylera is an antimicrobial tri-therapy that helps tackle H. pylori infections.
