Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Diagnostic Tool Aids Quality Control in Xenotransplantations

04.12.2017

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.


Flourescein—tagged Lectins a new probe for detecting sugars in pig cells.

© Beshir et al. 2017


PIIA complexed with the raffinose carbohydrate.

© Beshir et al. 2017

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.

Original publication:
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.

Weitere Informationen:

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

More articles from Life Sciences:

nachricht Designer cells: artificial enzyme can activate a gene switch
22.05.2018 | Universität Basel

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Designer cells: artificial enzyme can activate a gene switch

22.05.2018 | Life Sciences

PR of MCC: Carbon removal from atmosphere unavoidable for 1.5 degree target

22.05.2018 | Earth Sciences

Achema 2018: New camera system monitors distillation and helps save energy

22.05.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>