Selective killing of the human gastric pathogen Helicobacter pylori


Helicobacter pylori (H. pylori) is a type of bacterium that infects the stomach lining and is estimated to be present in over half of the world’s population. While H. pylori infection does not always cause noticeable symptoms, it is a major risk factor for the development of stomach cancer. H. pylori infection is believed to contribute to the development of stomach cancer by causing chronic inflammation of the stomach lining, which can lead to cellular damage and mutation. The bacterium is also known to produce an enzyme called urease, which helps it to survive in the acidic environment of the stomach by converting urea into ammonia. The production of ammonia by H. pylori can further damage the stomach lining and increase the risk of cancer development. Several studies have demonstrated a strong association between H. pylori infection and stomach cancer. In fact, it is estimated that approximately 80% of all cases of stomach cancer worldwide are caused by H. pylori infection. The risk of developing stomach cancer is thought to be highest in individuals who have chronic H. pylori infection and other risk factors, such as a family history of stomach cancer, smoking, and a diet high in salt and smoked or pickled foods.

The relationship between H. pylori and stomach cancer is complex, and researchers are still working to fully understand the mechanisms behind this association. However, it is clear that H. pylori infection is an important risk factor for the development of stomach cancer, and efforts to prevent and treat this infection may help to reduce the incidence of this deadly disease. Treatment of H. pylori infection involves a course of antibiotics and acid suppressants, which can eradicate the bacterium and reduce the risk of developing gastric cancer. More than four billion people worldwide are infected with the stomach bacterium, leading to more than 800,000 cases of stomach cancer every year. Because the bacterium is becoming increasingly resistant to current drugs, the World Health Organization (WHO) has classified 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 pathogen Helicobacter pylori, which is 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 German research group led by LMU biologists Professor Rainer Haas. Their results have now been published in the journal Cell Chemical Biology.

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. 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. The authors’ findings reveal a surprising weakness in the metabolism of these bacteria, which are well adapted otherwise to their unusual environment. The research team 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.

Finding a cure for H. pylori infection and preventing its associated cancer is of great importance because it reduces the incidence of stomach cancer. As mentioned earlier, H. pylori infection is a significant risk factor for stomach cancer. By treating and curing H. pylori infection, the risk of developing stomach cancer can be significantly reduced, which could potentially save many lives. Moreover, the treatment of stomach cancer can be expensive, and the economic burden on healthcare systems can be significant. By preventing H. pylori infection and subsequent stomach cancer, healthcare costs can be reduced. H. pylori infection can cause various gastrointestinal problems, such as ulcers and gastritis, which can significantly impact an individual’s quality of life. By curing H. pylori infection, these symptoms can be alleviated, leading to an improved quality of life. Antibiotics are commonly used to treat H. pylori infection, but overuse and misuse of antibiotics have led to the development of antibiotic-resistant strains of the bacterium. Finding a cure for H. pylori infection would reduce the need for antibiotics and thus help to combat antibiotic resistance. In summary, finding a cure for H. pylori infection and preventing its associated cancer is crucial for improving public health, reducing healthcare costs, improving quality of life, and combating antibiotic resistance. the authors 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.

Selective killing of the human gastric pathogen Helicobacter pylori - Medicine Innovates

About the author

Prof. Dr. rer. nat. Rainer Haas

Max von Pettenkofer-Institute

Research interests: Helicobacter pylori is a highly successful bacterial pathogen that infects the gastric mucosa of approximately 50% of the world’s population, leading to chronic gastritis or peptic ulceration and increasing the risk of gastric cancer. We are investigating the mechanisms of specific bacteria-host interactions and we study how these bacteria manipulate epithelial cells or the immune cell migration to cause gastric disease. Our group is focusing on the cag Type 4 secretion system (cag-T4SS) to investigate its structure and function as well as the molecular mechanism of CagA translocation. Bacterial outer membrane adhesins and their receptors on host cells, such as the carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) or integrins, are studied under in vitro and in vivo conditions using appropriate cell lines and a CEACAM-humanized mouse model. In addition, we also identify and characterize small molecule inhibitors (SMIs) interfering with the cag-T4SS and/or other vital functions of the bacterial pathogen.


Lettl C, Schindele F, Mehdipour AR, Steiner T, Ring D, Brack-Werner R, Stecher B, Eisenreich W, Bilitewski U, Hummer G, Witschel M, Fischer W, Haas R. Selective killing of the human gastric pathogen Helicobacter pylori by mitochondrial respiratory complex I inhibitors. Cell Chem Biol. 2023 Apr 20:S2451-9456(23)00089-2. doi: 10.1016/j.chembiol.2023.04.003.

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