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Researchers from the University of Tübingen and the German Center for Research on Infections (DZIF) have achieved a breakthrough in the decryption of multi-drug resistant disease germs. The team led by Professor Andreas Peschel and professor Thilo Stehle was able to explain the structure and function of the previously unknown protein, with which they feared pathogens, such as Staphylococcus aureus, protect against the human immune system, as with the invisibility cloak. The study was published on Wednesday in the journal Nature.
Infections with bacteria such as Staphylococcus aureus cause numerous deaths around the world. Especially fears in hospitals are antibiotic resistant methicillin, strains Staphylococcus aureus or MRSA in short. According to a study published in early November, in the EU alone in 2015, there were about 670,000 resistant to many drugs. 33,000 patients died.
The rule is that our immune system handles well pathogens, such as bacteria or viruses. In some germs, the defensive strategies of the human body fail, especially in immunocompromised patients. Unfortunately, antibiotics are ineffective against resistant pathogens. Effective preventive antibiotics and MRSA vaccines are not yet visible. A thorough understanding of defense mechanisms can allow new therapies against bacteria.
Researchers at the University of Tübingen have now described how MRSA are invisible to the immune system. They have proven that many of MRSA's particularly popular germs have acquired a previously unknown protein, meaning that pathogens are no longer recognized by antibodies to the immune system. The Tübingen researchers gave this protein the name TarP (short for P-ribonucleic acid).
"TarP changes the structure of sugar molecules on the surface of the pathogen in an unprecedented way," said Professor Andreas Peschel from the Interfaculty Institute of Microbiology and Medicine Infection at the University of Tübingen. "This means that the immune system can not produce antibodies to the most important MRSA antigen, i.e. dicofic acid." The immune system is therefore not only "blind." It also loses the most important weapon against the pathogen.
Reprogrammed by phages
Researchers in Tübingen assume that the bacterial mantle of invisibility is the result of a conflict between pathogens and their natural enemies, the so-called phages. Bacteriophage is a class of viruses that attack bacteria, uses them as a host cell and feeds on them. In this case, the phages apparently reprogrammed their host using TarP protein, thus changing the surface of the bacteria.
The first authors of the work, David Gerlach and Yinglan Guo, managed to explain the mechanism and structure of the TarP. "Now we understand in detail how the protein works at the molecular level as an enzyme," Gerlach said. The analysis of TarP function and structure is an excellent basis for the development of new active substances that block TarP and make the pathogen recognizable for the immune system. Particularly important for the success of this work was an interdisciplinary approach involving other scientists from Denmark, Germany, Great Britain, Italy, the Netherlands and South Korea.
"The discovery of TarP was a total surprise to us. It explains very well why the immune system often has no chance for MRSA," said Professor Thilo Stehle of the Inter-faculty Institute of Biochemistry. 'Available results will help us develop better therapies and vaccines against pathogens.' Peschel referred to the recently approved cluster of excellence in Tübingen "Controlling microorganisms to fight infections" and close involvement in the German Infection Research Center: "This excellent network of contacts will help us to further develop the exploration of MRSA and TarP."
High resolution photo on the website http://www.pressefotos.uni-tuebingen.de/2018-11-19_Staphylococcus aureus.zip
Pay attention to the source!
Professor Dr. Andreas Peschel
University of Tübingen
Inter-faculty Institute of Microbiology and Infectious Medicine
Phone +49 7071 29-78855
Professor Dr. Thilo Stehle
University of Tübingen
Inter-faculty Institute of Biochemistry
Phone +49 7071 29-73043
Gerlach, Guo et al., 2018, methicillin resistant Staphylococcus aureus, glycosylation of the cell wall at the age to avoid immunity. Nature, DOI: 10.1038 / s41586-018-0730-x (Only available after the expiry of the embargo: Wednesday, November 21, 2018, 19.00 Central European Time)