Molecular Infection Biology
Gastrointestinal infections are counted among the most common types of infectious diseases worldwide. In particular in developing countries, diarrhoeal diseases are still a leading course of death. Indeveloped countries, diarrhoeal diseases are under better control, but they still represent a very common affliction, especially among children and the elderly. Among the most important bacterial pathogens of food-animal origin are Salmonella, Shiga toxin-producing Escherichia coli, and enteropathogenic Yersinia species. Their primary route of transmission from animals to humans is through contaminated food. Once inside our bodies, they trigger an impressive range of different intestinal disorders from diarrhoea to acute infections of the small and large intestines – at times with severe consequences! Our primary focus is on Yersinia. We study the ways in which these bacteria adhere to the intestinal epithelium, penetrate it, and ultimately spread within the host.
In order to gain a comprehensive understanding of the molecular mechanisms underlying bacterial infection of the intestines, the Department of "Molecular Infection Biology" (MIBI) studies how enteropathogenic yersiniae adhere to the surface of the intestinal epithelium and migrate into cells of the epithelial layer. Bacterial attachment to the intestinal cells triggers a cascade of different reactions, including reorganization of the epithelial cells’ actin cytoskeleton to produce special kinds of membrane projections (filopodia). These filopodia surround the bacteria and enclosed them within the cell. This allows the bacteria to traverse the intestinal epithelium, migrate into the underlying lymphatic tissues, and spread to deeper tissues and organs. Not only do they manage to colonize the host’s tissues, they also successfully evade the host’s immune system.
The departments’ special research focus is on findings answers to the following questions:
- How do pathogenic microbes manage to attach to and enter eukaryotic cells?
- Which bacterial and host factors are involved and when do the cells produce these factors?
- When, where, and by what regulatory mechanisms are virulence factors produced as part of the infection process?
- How do pathogens adapt their metabolism during an infection?
In order to be able to answer these questions, we are studying the structure and function of virulence factors that are involved in bacterial entry into the host cells. As such, they characterize the different infection routes and signal transduction pathways triggered within the host cell, the timing of Yersinia’s attack, and the regulatory mechanisms behind the changes in gene expression in the pathogen and in the host.
One important signal that induces virulence gene expression during the infection is the temperature change the bacteria detect upon host entry. A central regulatory bacterial protein, which plays a key role in infection, acts as a protein thermometer. It changes its shape after a thermal upshift from 30°C in the environment to 37°C inside the host intestine, and fulfils a very different set of functions. In addition, RNA molecules (RNA thermoswitches) are capable of changing their molecular structure in response to temperature, thereby altering production of virulence factors.
- Bakterien mit Thermometer - Vom Kühlschrank in den Körper
Yersinien machen uns Bauchschmerzen. Wenn wir die Bakterien mit verseuchtem Fleisch zu uns nehmen, infizieren sie unsere Darmzellen und vermehren sich. Aber wie wissen die Yersinien, dass sie nicht mehr in der vergammelten Wurst sind sondern in unserem Körper? Die Antwort ist simpel: Die Bakterien haben ein Thermometer. Hören Sie zu, wie das funktioniert...