HZI and HIPS researchers discover a bacterial protein that recognises immunogenic sugar molecules on pig cells
Sugars are highly important molecules for all life. They convey vital signals, and thus participate in manifold biological processes (e.g. determination of blood-types and the formation of bacterial biofilms). Sugars are often recognized by specialized proteins called lectins.
Researchers at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), a branch of the Helmholtz Centre for Infection Research (HZI), recently identified a novel lectin in the bacterium Photorhabdus luminescens. This lectin is highly selective for so-called "α-gal" sugars, which are produced on the cells of pigs and New World monkeys.
Pig cells are often used for tissue grafts from pigs to humans, in which the transplanted pig cells need to be modified by genetic engineering in order to prevent a vigorous immune response to the α-gal (also called xenoantigen) normally found on pig cells. The newly discovered lectin may be used as a diagnostic tool and for quality control in the future. The researchers published their results in the Journal of Biological Chemistry.
Sugar-binding proteins called lectins are widespread in all domains of life and used as virulence factors in numerous bacteria, e.g. in Pseudomonas aeruginosa. Lectins make it easier for the microorganisms to adhere to the host for the purpose of infection.
This motivated Dr Alexander Titz, who is the head of the "Chemical Biology of Carbohydrates" junior research group of the Helmholtz Centre for Infection Research (HZI) and of the German Center for Infection Research (DZIF)who is the head of the "Chemical Biology of Carbohydrates" young researcher group at the HIPS, to compare lectins from different bacteria: "We wanted to find out if there are additional lectins in other types of bacteria that show high specificity forcertain sugars." His research group scoured sequence databases in the search for new lectins and found one in the bacterium Photorhabdus luminescens that piqued their interest.
Photorhabdus bacteria lead a symbiotic life in nematodes and infest larger organisms. "The Photorhabdus lectin surprisingly showed a very high specificity for the sugar structure α-gal that occurs in pigs and New World monkeys," says Alexander Titz. "After this discovery, we wanted to know exactly how this works."
Light was shed on this question through a collaboration with Dr Jesko Köhnke, who is the head of the "Structural Biology of Biosynthetic Enzymes" young investigator group at the HIPS. "We elucidated the crystal structure of the new lectin - bound to different sugars - in order to understand the binding properties of the molecule," says Köhnke.
The findings of the two research groups, which was driven by blue-sky research, has now serendipitously led to a clinical application as a diagnostic tool. The special sugar α-gal recognised by the Photorhabdus lectin plays an important role in organ transplantations of foreign tissues into humans.
Due to the lack of human organ donors, it is quite common to transplant tissues from pigs, for example heart valves. Pig cells usually have α-gal on their surface. This is recognised by the human immune system and leads to vigorous defence reactions of the human body in the form of acute organ/cell rejection. Modern genetic engineering methods have been used to produce pig cells that are void of α-gal on their surface. But the success of these methods must be closely monitored:
The Photorhabdus lectin may be used for quality control in this context in order to make sure that no α-gal is present. Until now, a lectin from seeds of an African plant called Griffonia simplicifolia was used for this purpose, the isolation of which is a complicated process. In contrast, the newly described lectin is comparatively easy and inexpensive to produce and has been tested successfully for these purposes by the research group of Prof Eckhard Wolf at the Veterinary Faculty of the Ludwig-Maximilians-University in Munich.
The HIPS researchers also do not rule out a broader use of the diagnostic tool for α-galactosylated sugars. "The ABO blood group system of humans is also defined by sugars. Here, the Photorhabdus lectin might be used as a new typing system," says Titz.
Ghamdan Beshr, Asfandyar Sikandar, Eva-Maria Jemiller, Nikolai Klymiuk, Dirk Hauck, Stefanie Wagner, Eckhard Wolf, Jesko Koehnke, Alexander Titz: Photorhabdus luminescens lectin A (PIIA) – a new probe for detecting α-galactoside-terminating glycoconjugates. Journal of Biological Chemistry, 2017, DOI: 10.1074/jbc.M117.812792
The Helmholtz Centre for Infection Research:
Scientists at the Helmholtz Centre for Infection Research (HZI) investigate the mechanisms of infections and of the defences against infections. What is it that makes bacteria or viruses pathogenic? The answer to this question is expected to be key to the development of new medications and vaccines.
http://www.jbc.org/content/early/2017/09/28/jbc.M117.812792 - publication
https://www.helmholtz-hzi.de/en/news_events/news/view/article/complete/new_diagn... - press release
http://www.helmholtz-hzi.de - Webpage HZI
Susanne Thiele | Helmholtz-Zentrum für Infektionsforschung
Lethal combination: Drug cocktail turns off the juice to cancer cells
12.12.2018 | Universität Basel
Smelling the forest – not the trees
12.12.2018 | Universität Konstanz
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...
What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.
Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...
Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.
Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
12.12.2018 | Health and Medicine
12.12.2018 | Physics and Astronomy
12.12.2018 | Health and Medicine