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Research determines how pathogens can outwit our immune system

Bacteria

16 Jul 2019

Advances in biotechnology from the University of Bonn, Germany, have determined  how an enzyme changes its shape and stimulate the infection.

Tiffany Hionas

The bacteria in Yersinia, which causes a bowel infection, injects various enzymes into the macrophages of the immune system where the enzymes, known as YopO, activate and prevent defence cells from enclosing and digesting the plague bacteria.

Until the discovery of antibiotics, Yersinia triggered a global wave of fear and terror, causing a total of 1451 deaths in 21 countries between 1978 and 1992, according to the World Health Organization (WHO).

This plague pathogen injects YopO and other enzymes into white blood cells, which is an important part of our immune system, known as the macrophages of the immune system. YopO is activated when it binds to the protein of the cell.

Normally, the structural protein actin helps the phagocyte, which is responsible for absorbing the bacteria, to dissolve the pathogens into small pieces. This process is meant to allow the macrophage to initiate an immune response.

However, once YopO attaches itself to the actin, it disrupts communication within the macrophage, preventing the macrophage from protecting the body. Researchers are still investigating the structure of the actin-bound YopO and it remains unclear as to how the YopO can change its shape when it binds to the actin.

Dr Gregor Hagelüken from the University of Bonn explained that ‘enzymes are not stiff structures but have several mobile ‘hinges’ with which they can change their shape.’

The scientists at the University of Bonn used several instruments, including the PETRA III accelerator of the German Electron Synchrotron DESY, to create a series of intense and focused x-rays which can be used to study the overall structure and structural changes of enzymes.

The team then attached spin markers to certain points on the YopO and actin, which allows the researchers to use a molecular ruler known the PELDOR method, allowing one to investigate how YopO and actin change shape.

Martin Peter from the University of Bonn, lead author of this study, said that the ‘results strongly indicate, however, that it is not a larger movement, but many small ones, with which YopO enters the active state.’

Dr Hagelüken concluded: ‘Bacteria can become resistant if antibiotics are used frequently, which means that the drugs no longer work properly.’

It is pivotal that research is underway to better understand the processes of pathogens, and how they work to outwit the immune system, which will better inform research to create more tailor-made substances to fight off pathogens.

DOI: 10.1016/j.str.2019.06.007

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