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Researchers at the University of Tübingen and the German Infection Research Center (DZIF) have achieved a breakthrough in the decryption of germs that are resistant to various drugs. The team led by Professor Andreas Peschel and Professor Thilo Stehle were able to explain the structure and function of previously unknown proteins, with the help of feared pathogens such as Staphylococcus aureus protecting against the human immune system such as invisibility cloaks. The study was published Wednesday in the journal Nature.
Infection by bacteria such as Staphylococcus aureus causes many deaths worldwide. The most feared in hospitals are strains that are resistant to the antibiotic methicillin, Staphylococcus aureus, or MRSA for the short term. According to a study published in early November, there were around 670,000 drug-resistant pathogens in the European Union alone in 2015. 33,000 patients died.
As a rule, our immune system works well with pathogens such as bacteria or viruses. But in some germs, the human body's defense strategy fails, especially in patients with immune disorders. Unfortunately, antibiotics are not effective against resistant pathogens. Effective replacement antibiotics and protective vaccines against MRSA have not been seen. An accurate understanding of defense mechanisms can enable new therapies against bacteria.
Researchers at the University of Tübingen have now explained how MRSA germs are not visible to the immune system. They were able to show that many common MRSA germs have obtained previously unknown proteins, which means that pathogens are no longer recognized by immune system antibodies. The Tübingen scientists gave protein the name TarP (short for ribitol acid P).
"TarP changes the pattern of sugar molecules on the surface of pathogens in ways that have never been seen before," said Professor Andreas Peschel of the Interfaculty of the Institute for Microbiology and Infection Medicine at the University of Tubingen. "This means that the immune system cannot produce antibodies to the most important MRSA antigen, dicofiallic acid." Thus the immune system is not only "blind". It also loses the most important weapons against pathogens.
Reprogrammed by phages
The Tübingen researchers assume that the cloak of invisibility bacteria is the result of conflicts between pathogens and their natural enemies, called phages. Bacteriophage is a class of viruses that attack bacteria, use it as a host cell and eat it. In this case, phages apparently reprogram their hosts using TarP proteins, thus changing the surface of the bacteria.
The first author of the work, David Gerlach and Yinglan Guo, succeeded in clarifying the mechanism and structure of TarP. "We now understand in detail how proteins work at the molecular level as enzymes," Gerlach said. TarP's structure-function analysis forms an excellent basis for the development of new active substances that inhibit TarP and make pathogens recognized in the immune system. Very important for the success of this work is an interdisciplinary approach, in which other scientists from Denmark, Germany, Britain, Italy, the Netherlands and South Korea are involved.
"TarP's discovery came as a surprise to us. This explains well why the immune system often has no chance against MRSA," said Professor Thilo Stehle of the Interfaculty Institute of Biochemistry. "The results now available will help us to develop therapies and vaccines that are better against pathogens." Peschel refers to the Tubingen Cluster of Excellence that was recently approved "Controlling Microbes to Combat Infection" and close involvement at the German Infection Research Center: "This excellent network will help us further advance the exploration of MRSA and TarP."
High resolution images at http://www.pressefotos.uni-tuebingen.de/2018-11-19_Staphylococcus aureus.zip
Please pay attention to the source!
Prof. Dr. Andreas Peschel
University of Tübingen
Interfaculty Institute of Microbiology and Infection Medicine
Phone +49 7071 29-78855
Prof. Dr. Thilo Stehle
University of Tübingen
Interfaculty Institute of Biochemistry
Phone +49 7071 29-73043
Gerlach, Guo et al., 2018, Methicillin-resistant Staphylococcus aureus glycosylated age cell walls to avoid immunity. Nature, DOI: 10.1038 / s41586-018-0730-x (Only available after the embargo ends: Wednesday, November 21, 2018, 7:00 CET)