Technical University of Munich Develops Highly Effective Drug Candidate Targeting Helicobacter pylori to Reduce Stomach Cancer Risk

The dangerous bacterium Helicobacter pylori under a microscope. Image credit: Raquel Mejías Luque / TUM

(IN BRIEF) Researchers at the Technical University of Munich have developed a new drug candidate that significantly enhances the effectiveness of the antibiotic metronidazole against Helicobacter pylori, a bacterium linked to stomach cancer. By introducing targeted chemical modifications, the team created compounds that are up to 60 times more effective in laboratory tests and show strong activity against antibiotic-resistant strains. The new approach works by simultaneously inducing oxidative stress and disrupting key bacterial defense mechanisms. Preclinical studies in mice demonstrated complete eradication of the infection at low doses while preserving the gut microbiome, and no increased toxicity was observed in human cells. Although further clinical trials are required, the findings represent a promising advancement in the prevention and treatment of H. pylori-related diseases.

(PRESS RELEASE) MUNICH, 18-Mar-2026 — /EuropaWire/ — Technical University of Munich researchers have developed a promising new drug candidate that significantly enhances the effectiveness of a commonly used antibiotic against the bacterium Helicobacter pylori, offering new potential in the prevention of stomach cancer.

The research team, led by Prof. Stephan A. Sieber, achieved a major breakthrough by modifying the antibiotic metronidazole at a molecular level. Through targeted chemical adjustments, they created new compounds—known as ether derivatives—that demonstrated up to 60 times greater effectiveness in combating H. pylori in laboratory studies.

H. pylori infects approximately 43 percent of the global population and is a major contributor to chronic stomach inflammation, ulcers, and gastric cancer. Traditional treatments rely heavily on metronidazole, but increasing resistance among bacterial strains has reduced its effectiveness, often requiring higher doses or combination therapies.

The TUM researchers investigated the antibiotic’s mechanism in greater depth and identified an additional mode of action beyond its known ability to induce oxidative stress. Their findings revealed that metronidazole also disrupts two critical protective systems within the bacterium: an enzyme responsible for neutralizing harmful reactive oxygen species and a protein involved in repairing damaged cellular structures. By targeting these mechanisms simultaneously, the modified compounds weaken the bacterium’s ability to survive under stress.

According to study contributors Dr. Michaela Fiedler and Marianne Pandler, the optimized molecules bind more effectively to their biological targets, enhancing antibacterial activity. This improved binding capacity allows the drug candidate to more efficiently eliminate H. pylori by overwhelming its defense systems.

Laboratory experiments confirmed the enhanced performance of the modified compounds, showing strong activity not only against standard strains but also against antibiotic-resistant variants. Importantly, the researchers observed no increased toxicity to human cells, indicating a favorable safety profile at this stage of development.

In preclinical animal studies, the results were equally promising. Tests conducted in mice demonstrated complete eradication of H. pylori infections at low doses, while also preserving the gut microbiome more effectively than current standard treatments.

Prof. Sieber noted that while the findings represent a significant advance, further validation through human clinical trials will be necessary. If confirmed, the new drug candidate could represent a major step forward in reducing the global burden of stomach cancer and improving treatment outcomes for H. pylori infections.

The study was published in Nature Microbiology and involved contributions from additional researchers, including Prof. Michael Groll and Prof. Markus Gerhard, highlighting a collaborative effort across multiple scientific disciplines within TUM.

Publications

Michaela K. Fiedler, Marianne S. I. Pandler et al.: “Metronidazole and ether derivatives target Helicobacter pylori via simultaneous stress induction and inhibition,” published in Nature Microbiology, 2026. DOI: 10.1038/s41564-026-02291-w

Further information and links

In addition to Prof. Sieber, Prof. Michael Groll, Chair of Biochemistry at the TUM School of Natural Sciences, and Prof. Markus Gerhard from the Institute of Medical Microbiology, Immunology and Hygiene at the TUM School of Medicine and Health, were closely involved in the research.

SOURCE: Technical University of Munich