Sunday, 25 August 2019

How plague pathogens trick the immune system

Yersinia plague bacterium

Yersinia have spread fear and terror, especially in the past, but today the plague pathogens have still not been completely eradicated. The bacteria inject various enzymes, including the enzyme YopO, into the macrophages of the immune system. There it is activated and prevents the defense cells from enclosing and digesting the plague bacteria. Using the latest methods, scientists from the Institute of Physical and Theoretical Chemistry at the University of Bonn have now deciphered how YopO changes its shape and thus contributes to confusing the immune system. The results have now been published in the journal Structure.

Yersinia also includes the plague pathogen, which caused fear and terror worldwide until the discovery of antibiotics. The major epidemics are over, but the World Health Organization (WHO) reported a total of 1451 deaths in 21 countries between 1978 and 1992. Plague bacteria are also found in wild rodents. The transmission occurs mainly via fleas, but also via droplet infection. "Yersinia trick the macrophages of the immune system," says Dr. Gregor Hagel√ľken from the Institute of Physical and Theoretical Chemistry at the University of Bonn.

The structural biologist has already done research in Yersinia as a PhD student at the Helmholtz Centre for Infection Research in Braunschweig. The special feature of the plague pathogens is a kind of syringe with which they inject the YopO and some other enzymes into the macrophages of the immune system. However, YopO only becomes active when it binds to the actin of the scavenger cell. Normally, the structural protein actin helps the phagocyte to form protrusions with which it flows around the pathogens and then disolves them into small pieces. During this process, the macrophage calls for help from other defense cells.

The scientists at the University of Bonn therefore used several instruments from the structural elucidation toolbox. Together with Dr. Dmitri Svergun from the European Molecular Biology Laboratory in Hamburg, they used the PETRA III electron accelerator of the German Electron Synchrotron DESY. "The extremely intense and focused X-rays can be used to study the overall structure and structural changes of enzymes dissolved in water with the aid of small-angle X-ray scattering," said Svergun.


In addition, the researchers attached spin markers to certain positions of YopO and actin. These function like survey points in the landscape at which, for example, the exact location of a property can be determined. "Using the spin markers, we can use a molecular ruler -- the PELDOR method -- to measure the nanometer distances between these positions and thus determine how YopO and actin change shape," reports Hagel√ľken. So far it has been presumed that YopO performs a folding movement like scissors as soon as it binds to actin.

See:

Martin F. Peter, Anne T. Tuukkanen, Caspar A. Heubach, Alexander Selsam, Fraser G. Duthie, Dmitri I. Svergun, Olav Schiemann, Gregor Hagelueken. Studying Conformational Changes of the Yersinia Type-III-Secretion Effector YopO in Solution by Integrative Structural Biology. Structure, 2019; DOI: 10.1016/j.str.2019.06.007

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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