Multi-resistant bacteria with camouflage strategy

A previously unknown protein makes Staphylococcus aureus pathogens invisible to the immune system.

A new approach has been uncovered for treating infections caused by particularly dangerous bacte-ria. Researchers at the University of Tübingen and the German Center for Infection Research (DZIF) have teamed up with scientists from the Max Planck Institute for Colloids and Interfaces and have achieved a breakthrough in determining how Staphylococcus aureus evades detection by the immune system. According to them, a previously unknown protein helps the pathogen, which can cause life-threatening infections in hospitals, to avoid detection, as if hidden by a magic cloak. The researchers have now identified the structure and function of this protein, thereby creating a basis for allowing the immune system to recognise this pathogen.

Infections caused by bacteria such as Staphylococcus aureus cause many deaths worldwide. Staphylococcus aureus strains resistant to the antibiotic methicillin (MRSA for short) are particularly feared in hospitals. According to a study published at the beginning of November, there were around 670,000 diseases caused by multi-resistant pathogens in the EU alone in 2015 and 33,000 patients died.

Normally, our immune system copes well with many pathogens such as bacteria or viruses. However, in the case of some pathogens, sometimes the defensive strategies of the human body fail, especially in immunocompromised patients. Meanwhile even the most effective antibiotics are ineffective against resistant pathogens. Effective replacement antibiotics and a protective vaccine against MRSA are not yet in sight. The international team from the University of Tübingen and DZIF have now contributed to a better understanding of how some bacteria are missed by the immune system and this may lead to new treatments to tackle the bacteria.

The protein TarP prevents the formation of antibodies

Scientists have now described how MRSA bacteria become invisible to the immune system. They were able to show that many of the particularly frequent MRSA bacteria have acquired a previously unknown protein that prevents the pathogens from being detected by antibodies in the immune system. The Tübingen scientists gave the protein the name TarP (short for teichoic acid ribitol P).

“TarP alters the pattern of sugar molecules on the pathogen surface in a previously unknown way,” explained Professor Andreas Peschel from the Interfaculty Institute of Microbiology and Infection Medicine at the University of Tübingen. “As a result, the immune system is unable to produce antibodies against the most important MRSA antigen, teichoic acid,” said Peschel. “The immune system is ‘blinded’ and loses its most important weapon against the pathogen.”

Reprogrammed by phages

The researchers from Tübingen assume that the bacterial camouflage is the result of an exchange between the pathogens and their natural enemies, known as phages. Bacteriophages are a class of viruses that attack bacteria, use them as host cells and feed on them. In this case, phages seem to have reprogrammed their host using the TarP protein and thus altered the surface of the bacterium.

The first authors of the study, David Gerlach and Yinglan Guo, succeeded in clarifying the mechanism and structure of TarP. “We now have a detailed understanding of how the protein functions as an enzyme on the molecular level,” said Gerlach. The structure-function analysis of TarP forms an excellent basis for the development of new drugs that block TarP, allowing the immune system to detect the pathogens again.  An interdisciplinary approach, involving scientists from Denmark, Germany, Great Britain, Italy, the Netherlands and South Korea, was particularly important for the success of this work. Scientists led by Peter Seeberger, Director of the Max Planck Institute for Colloids and Interfaces, provided the key to the structural analysis of the detection process with synthetic glycans.

“The discovery of TarP came as a complete surprise to us. It explains very well why the immune system often has no chance against MRSA,” said Professor Thilo Stehle from the Interfaculty Institute of Biochemistry. “The results will help us to develop better therapies and vaccines against the pathogens.”

Uni Tübingen/PH