Press releases

A team from Research Unit 2251 of the German Research Foundation led by Goethe University has shed light on the structure of an enzyme important in the metabolism of the pathogenic bacterium Acinetobacter baumannii. The enzyme “MtlD" is critical for the bacterium's synthesis of the sugar alcohol mannitol, with which it protects itself against water loss and desiccation in dry or salty environments such as blood or urine. Structural analysis has revealed weak spots where it might be possible to inhibit the enzyme and thus attack the pathogen. (PNAS, DOI: 10.1073/pnas.2107994119)

FRANKFURT. Each year, over 670,000 people in Europe fall ill through pathogenic bacteria that are resistant to antibiotics, and 33,000 die of the diseases they cause. In 2017, the WHO named antibiotic resistance as one of the greatest threats to health worldwide. Especially feared are pathogens that are resistant to several antibiotics. Among them, Acinetobacter baumannii stands out, a bacterium with an extraordinarily pronounced ability to develop multiresistance and, as a “hospital superbug", dangerous above all for immunosuppressed patients. Acinetobacter baumannii is highly resilient because it can remain infectious for a long time even in a dry environment and thus endure on the keyboards of medical devices or on ward telephones and lamps. This property also helps the microbe to survive on dry human skin or in body fluids such as blood and urine, which contain relatively high concentrations of salts and other solutes.

The team from Research Unit 2251 of the German Research Foundation led by Goethe University has now shed light on a central mechanism via which Acinetobacter baumannii settles in such an adverse environment: like many bacteria as well as plants or fungi, Acinetobacter baumannii is able to synthesize the sugar alcohol mannitol, a substance excellent at binding water. In this way, Acinetobacter baumannii prevents desiccation.

Almost unique, however, is the way that Acinetobacter baumannii synthesizes mannitol: instead of two enzyme complexes as are common in most organisms, the two last steps in mannitol synthesis are catalysed by just one. A team of researchers led by Professor Beate Averhoff and Professor Volker Müller already discovered this “MtlD" enzyme with two catalytic activities back in 2018. The team headed by Professor Klaas Martinus Pos, who is also a member of the Research Unit, has now succeeded in shedding light on the enzyme's spatial structure.

He explains: “We've discovered that the enzyme is usually present in the form of free monomers. Although these have the necessary catalytic activities, they are inactive. Only a dry or salty environment triggers what is known as 'osmotic stress' in the bacterium, after which the monomers aggregate as dimers. Only then does the enzyme become active and synthesize mannitol." The researchers have also identified which parts in the structure are particularly important for the enzyme's catalytic functions and for dimer formation.

Professor Volker Müller, spokesperson for Research Unit 2251, is convinced: “Our work constitutes an important new approach for fighting this hospital pathogen since we've identified a biochemically sensitive point in the pathogen's metabolism. In the future, this could be the starting point for customized substances to inhibit the enzyme."

Publication: Heng-Keat Tam, Patricia König, Stephanie Himpich, Ngoc Dinh Ngu, Rupert Abele, Volker Müller, Klaas M. Pos: Unidirectional mannitol synthesis of Acinetobacter baumannii MtlD is facilitated by the helix-loop-helix-mediated dimer formation. Proc. Natl. Acad. Sci. U.S.A. (2022) https://www.pnas.org/doi/full/10.1073/pnas.2107994119

Picture download:

1) Mannitol-Synthesizing Enzyme
https://www.uni-frankfurt.de/116943466
Caption: Resembles a butterfly: only in its dimer form does the mannitol-synthesizing enzyme of the hospital pathogen Acinetobacter baumannii protect the bacterium from water loss and desiccation. Picture: Klaas Martinus Pos, Goethe University Frankfurt

2) Acinetobacter baumannii
https://commons.wikimedia.org/wiki/File:Acinetobacter_baumannii.JPGCaption: Scanning electron micrograph (SEM) of a highly magnified cluster of Gram-negative, non-motile Acinetobacter baumannii bacteria. Photo: Janice Carr

Further information:
Professor Volker Müller
Research Unit 2251 Spokesperson
Department of Molecular Microbiology & Bioenergetics
Institute for Molecular Biosciences
Goethe University Frankfurt, Germany
Tel.: +49 (0)69 798-29507
vmueller@bio.uni-frankfurt.de

Professor Klaas Martinus Pos
Membrane Transport Machineries Group
Institute of Biochemistry
Goethe University Frankfurt, Germany
Tel.: +49 (0)69 798-29251
pos@em.uni-frankfurt.de

In Central and South America, predatory blood-sucking bugs transmit the causative agent of the widely prevalent Chagas disease. As the disease can induce severe symptoms and to date there is no vaccine against the Trypanosoma parasites, the main approach at present is to control the bug using insecticides. A German-Brazilian research team has now studied how trypanosomes change the bug's intestinal microbiota. The long-term goal: to change the bacterial community in the predatory bug's intestine in such a way that it can defend itself against the trypanosomes.

FRANKFURT. According to estimates by the World Health Organization (WHO), between six and seven million people worldwide, predominantly in Central and South America, are infected with the Trypanosoma cruzi species of trypanosome. This single-celled (protozoan) parasite causes Chagas disease (American trypanosomiasis), which in the acute phase is inconspicuous: only in every third case does the infected person develop any symptoms at all, which can then be unspecific, such as fever, hives and swollen lymph nodes. However, the parasites remain in the body, and many years later chronic Chagas disease can become life-threatening, with pathological enlargement of the heart and progressive paralysis of the gastrointestinal tract. 

There is no vaccine against the pathogen and treating the disease in the advanced stage is difficult. That is why the focus in Latin America is rather on controlling the bug that transmits Chagas trypanosomes: the predatory blood-sucking bug of the insect subfamily Triatominae. It ingests the trypanosomes during the sting, which then colonize its intestine. Through its faeces that it mostly deposited next to the bite, the bug excretes the pathogen, which is often rubbed into the wound when scratching the extremely itchy bite.

Although the number of new infections has dropped in various regions where insecticides are sprayed on a wide scale, problems are emerging: over the last decade, resistance to common insecticides by several species of predatory bugs has been increasingly observed. These insecticides also have a negative impact on the environment and the local population.

Researchers worldwide are making intense efforts to find alternative methods to help control Trypanosoma cruzi. One possibility might be to modify bacteria in the predatory bug's intestine in such a way that they eliminate the Chagas trypanosomes or inhibit their development.

In collaboration with scientists at the Instituto René Rachou in Belo Horizonte, Brazil, parasitologists and infection biologists Fanny Eberhard and Professor Sven Klimpel from Goethe University, the Senckenberg – Leibniz Institution for Biodiversity and Earth System Research (SGN) and the LOEWE Centre for Translational Biodiversity Genomics have now investigated how Chagas trypanosomes change the bacterial community in the predatory bug's intestine. To do so, they used genome analysis, which allowed them to compare the composition of the bacterial community in the bug's intestine, the microbiome, before and after infection with the pathogen (metagenomic shotgun sequencing).

The result: after the infection, the range of bacterial strains in the bug's intestine significantly decreased. Certain strains, including the potentially pathogenic bacterium Enterococcus faecalis, profited from the parasites' presence. Moreover, the researchers succeeded in identifying four bacterial species that probably take on functions important for the bug, such as the synthesis of B vitamins.

Fanny Eberhard explains: “Vitamin B is one of the nutrients that blood-sucking insects do not obtain through their blood meals. Bacteria that produce vitamin B are therefore very important for the bug, are found in practically all individuals and stay in the predatory bug's intestine even across generations. Hence, such bacteria are potentially suitable recipients for genes that produce defensive substances against Chagas trypanosomes."

Professor Sven Klimpel elaborates: “Ultimately, our goal is for the predatory bug to defend itself against Chagas trypanosomes and, in this way, to prevent infection in humans. However, before we can produce bacteria with such properties and then release predatory bugs containing them, we need to understand better how the ecology of the bug's intestine is structured and how the extensive interactions between host, pathogen and microbiome function. Our work is delivering an essential contribution to this."

Publication: Fanny E. Eberhard, Sven Klimpel, Alessandra A. Guarneri, Nicholas J. Tobias. Exposure to Trypanosoma parasites induces changes in the microbiome of the Chagas disease vector Rhodnius prolixus. Microbiome (2022) 10:45. https://doi.org/10.1186/s40168-022-01240-z

Picture download: https://www.uni-frankfurt.de/116081371

Captions:
Rhodnius prolixus_1000px.jpg
The predatory bug Rhodnius prolixus is one of the main vectors of Chagas disease in the north of South America and in Central America. Photo: Dr Erwin Huebner, University of Manitoba, Winnipeg, Canada/ Wikimedia Commons

Rhodnius prolixus_Life_cycle.jpg
Example of the hemimetabolic life cycle of the predatory triatomine bug Rhodnius prolixus. Shown are the adult vector, freshly laid, milky-white eggs, mature, reddish eggs and five nymphs. Red arrows mark a blood meal for the moulting process and egg production. Pictured in the middle are frequent hosts, such as dogs, opossums and humans. Graphics: Fanny E. Eberhard

Further information:
Professor Sven Klimpel
Institute of Ecology, Diversity and Evolution, Goethe University
Senckenberg – Leibniz Institution for Biodiversity and Earth System Research (SGN)
LOEWE Centre for Translational Biodiversity Genomics
Tel. +49 (0)69 798-42249
Klimpel@bio.uni-frankfurt.de
https://www.bio.uni-frankfurt.de/43925886/Abt__Klimpel

The POLY research group on premodern Christianities at Goethe University is offering five fellowships to Ukrainian academics specialised in medieval or early modern history.

FRANKFURT. The Russian attack on Ukraine is endangering the lives and work of many researchers. To help some of them to continue their research outside Ukraine, the “Polycentricity and Plurality of Premodern Christianities” (POLY) research group, a Centre for Advanced Studies in Humanities funded by the German Research Foundation, is offering five fellowships. These are intended for scholars with a doctoral degree who are dealing with medieval or early modern history and focus especially on religious diversity.

“With this initiative, we at POLY want to help colleagues from Ukraine forced to flee to safety and to give a stronger voice to Ukrainian science and research,” says Professor Birgit Emich, chair of the POLY fellowship programme, summing up the research group’s motivation. For Emich, who teaches early modern history at Goethe University, the fellowships also offer great opportunities for research in Frankfurt: “With the help of these visiting scholars, we aim to develop further partnerships in this region, which is so rich for the study of religious diversity.”

The fellowships are endowed with €3,000 per month and initially limited to four months. During the funding period, the visiting Ukrainian scholars will not only be integrated in work within POLY but also profit from other research infrastructure at Goethe University, notably, the research alliance “Dynamics of Religion”, co-chaired by Emich and Christian Wiese, theologian and professor for Jewish studies.

Applications for fellowships are now being accepted. They are conditional on a completed doctoral degree and an academic focus on religious plurality in the medieval or early modern period.

Further information
Professor Birgit Emich
Institute of History
Chair of Early Modern History
Goethe University
Tel.: +49 (0) 69 798-32594
Email: emich@em.uni-frankfurt.de
https://www.geschichte.uni-frankfurt.de/92594738/Polycentricity_and_Plurality_of_Premodern_Christianities__POLY

Editor: Dr. Anke Sauter, Science Editor, PR & Communication Office, Tel. +49 69 798-13066, Fax + 49 69 798-763-12531, sauter@pvw.uni-frankfurt.de

Computer chips and storage elements are expected to function as quickly as possible and be energy-saving at the same time. Innovative spintronic modules are at an advantage here thanks to their high speed and efficiency, as there is no lossy electrical current, rather the electrons couple with one another magnetically – like a series of tiny magnetic needles which interact with almost no friction loss. A team of scientists involving Goethe University Frankfurt and the Fritz Haber Institute in Berlin has now found promising properties with crystals grown from rare-earth atoms, which offer hope on the long path towards usage as spintronic components.

FRANKFURT. While modern computers are already very fast, they also consume vast amounts of electricity. For some years now a new technology has been much talked about, which although it is still in its infancy could one day revolutionise computer technology – spintronics. The word is a portmanteau meaning “spin” and “electronics”, because with these components electrons no longer flow through computer chips, but the spin of the electrons serves as the information carrier. A team of researchers with staff from Goethe University Frankfurt has now identified materials that have surprisingly fast properties for spintronics. The results have been published in the specialist magazine “Nature Materials”.

“You have to imagine the electron spins as if they were tiny magnetic needles which are attached to the atoms of a crystal lattice and which communicate with one another,” says Cornelius Krellner, Professor for Experimental Physics at Goethe University Frankfurt. How these magnetic needles react with one another fundamentally depends on the properties of the material. To date ferromagnetic materials have been examined in spintronics above all; with these materials – similarly to iron magnets – the magnetic needles prefer to point in one direction. In recent years, however, the focus has been placed on so-called antiferromagnets to a greater degree, because these materials are said to allow for even faster and more efficient switchability than other spintronic materials.

With antiferromagnets the neighbouring magnetic needles always point in opposite directions. If an atomic magnetic needle is pushed in one direction, the neighbouring needle turns to face in the opposite direction. This in turn causes the next but one neighbour to point in the same direction as the first needle again. “As this interplay takes place very quickly and with virtually no friction loss, it offers considerable potential for entirely new forms of electronic componentry,” explains Krellner.

Above all crystals with atoms from the group of rare earths are regarded as interesting candidates for spintronics as these comparatively heavy atoms have strong magnetic moments – chemists call the corresponding states of the electrons 4f orbitals. Among the rare-earth metals – some of which are neither rare nor expensive – are elements such as praseodymium and neodymium, which are also used in magnet technology. The research team has now studied seven materials with differing rare-earth atoms in total, from praseodymium to holmium.

The problem in the development of spintronic materials is that perfectly designed crystals are required for such components as the smallest discrepancies immediately have a negative impact on the overall magnetic order in the material. This is where the expertise in Frankfurt came into play. “The rare earths melt at about 1000 degrees Celsius, but the rhodium that is also needed for the crystal does not melt until about 2000 degrees Celsius,” says Krellner. “This is why customary crystallisation methods do not function here.”

Instead the scientists used hot indium as a solvent. The rare earths, as well as the rhodium and silicon that are required, dissolve in this at about 1500 degrees Celsius. The graphite crucible was kept at this temperature for about a week and then gently cooled. As a result the desired crystals grew in the form of thin disks with an edge length of two to three millimetres. These were then studied by the team with the aid of X-rays produced on the Berlin synchrotron BESSY II and on the Swiss Light Source of the Paul Scherrer Institute in Switzerland.

“The most important finding is that in the crystals which we have grown the rare-earth atoms react magnetically with one another very quickly and that the strength of these reactions can be specifically adjusted through the choice of atoms,” says Krellner. This opens up the path for further optimisation – ultimately spintronics is still purely fundamental research and years away from the production of commercial components.

There are still a great many problems to be solved on the path to market maturity, however. Thus, the crystals – which are produced in blazing heat – only deliver convincing magnetic properties at temperatures of less than minus 170 degrees Celsius. “We suspect that the operating temperatures can be raised significantly by adding iron atoms or similar elements,” says Krellner. “But it remains to be seen whether the magnetic properties are then just as positive.” Thanks to the new results the researchers now have a better idea of where it makes sense to change parameters, however.

Publication: Y. W. Windsor, S.-E. Lee, D. Zahn, V. Borisov, D. Thonig, K. Kliemt, A. Ernst, C. Schüßler-Langeheine, N. Pontius, U. Staub, C. Krellner, D. V. Vyalikh, O. Eriksson, L. Rettig: Exchange scaling of ultrafast angular momentum transfer in 4f antiferromagnets. Nature Materials (2022) https://www.nature.com/articles/s41563-022-01206-4

Further Information:
Prof. Dr. Cornelius Krellner
Crystal and Materials Laboratory
Institute of Physics
Phone: +49 (0)69 798-47295
krellner@physik.uni-frankfurt.de

An international team of scientists at the European XFEL has taken a snapshot of a cyclic molecule using a novel imaging method. Researchers from the European XFEL, DESY, Universität Hamburg and the Goethe University Frankfurt and other partners used the world's largest X-ray laser to explode the molecule iodopyridine in order to construct an image of the intact molecule from the resulting fragments. (Nature Physics, DOI 10.1038/s41567-022-01507-0).

SCHENEFELD/FRANKFURT. Exploding a photo subject in order to take its picture? An international research team at the European XFEL, the world's largest X-ray laser, applied this “extreme" method to take pictures of complex molecules. The scientists used the ultra-bright X-ray flashes generated by the facility to take snapshots of gas-phase iodopyridine molecules at atomic resolution. The X-ray laser caused the molecules to explode, and the image was reconstructed from the pieces. “Thanks to the European XFEL's extremely intense and particularly short X-ray pulses, we were able to produce an image of unprecedented clarity for this method and the size of the molecule," reports Rebecca Boll from the European XFEL, principal investigator of the experiment and one of the two first authors of the publication in the scientific journal Nature Physics in which the team describes their results. Such clear images of complex molecules have not been possible using this experimental technique until now.

The images are an important step towards recording molecular movies, which researchers hope to use in the future to observe details of biochemical and chemical reactions or physical changes at high resolution. Such films are expected to stimulate developments in various fields of research. “The method we use is particularly promising for investigating photochemical processes," explains Till Jahnke from the European XFEL and the Goethe University Frankfurt, who is a member of the core team conducting the study. Such processes in which chemical reactions are triggered by light are of great importance both in the laboratory and in nature, for example in photosynthesis and in visual processes in the eye. “The development of molecular movies is fundamental research," Jahnke explains, hoping that “the knowledge gained from them could help us to better understand such processes in the future and develop new ideas for medicine, sustainable energy production and materials research."

In the method known as Coulomb explosion imaging, a high-intensity and ultra-short X-ray laser pulse knocks a large number of electrons out of the molecule. Due to the strong electrostatic repulsion between the remaining, positively charged atoms, the molecule explodes within a few femtoseconds – a millionth of a billionth of a second. The individual ionised fragments then fly apart and are registered by a detector.

"Up to now, Coulomb explosion imaging was limited to small molecules consisting of no more than five atoms," explains Julia Schäfer from the Center for Free-Electron Laser Science (CFEL) at DESY, the other first author of the study. "With our work, we have broken this limit for this method." Iodopyridine (C5H4IN) consists of eleven atoms.

The film studio for the explosive molecule images is the SQS (Small Quantum Systems) instrument at the European XFEL. A COLTRIMS reaction microscope (REMI) developed especially for these types of investigations applies electric fields to direct the charged fragments onto a detector. The location and time of impact of the fragments are determined and then used to reconstruct their momentum – the product of mass and velocity – with which the ions hit the detector. “This information can be used to obtain details about the molecule, and with the help of models, we can reconstruct the course of reactions and processes involved," says DESY researcher Robin Santra, who led the theoretical part of the work.

Coulomb explosion imaging is particularly suitable for tracking very light atoms such as hydrogen in chemical reactions. The technique enables detailed investigations of individual molecules in the gas phase, and is therefore a complementary method for producing molecular movies, alongside those being developed for liquids and solids at other European XFEL instruments.

“We want to understand fundamental photochemical processes in detail. In the gas phase, there is no interference from other molecules or the environment. We can therefore use our technique to study individual, isolated molecules," says Jahnke. Boll adds: “We are working on investigating molecular dynamics as the next step, so that individual images can be combined into a real molecular movie, and have already conducted the first of these experiments."

The investigations involved researchers from Universität Hamburg, the Goethe University Frankfurt, the University of Kassel, Jiao Tong University in Shanghai, Kansas State University, the Max Planck Institutes for Medical Research and for Nuclear Physics, the Fritz Haber Institute of the Max Planck Society, the US accelerator laboratory SLAC, the Hamburg cluster of excellence CUI: Advanced Imaging of Matter, the Center for Free-Electron Laser Science at DESY, DESY and the European XFEL.

Publication: Rebecca Boll, Julia M. Schäfer, et al. X-ray multiphoton-induced Coulomb explosion images complex single molecules. Nature Physics, 2022, https://www.nature.com/articles/s41567-022-01507-0

Picture download:
https://media.xfel.eu/XFELmediabank/?language=en#l=en&cid=26753&cname=Coulomb-Explosion%20(20.01.2022)&f=&s=&p=&r=

Captions:
Model of the molecule Iodopyridine (molecule_A.jpg):
The ring is formed by carbon atoms (grey) and a nitrogen atom (blue). The iodine atom (violet) is on the outside of the ring. Credit: European XFEL / Rebecca Boll, Till Jahnke

Coulomb Explosion Imaging of hydrogen atoms (protons_B.jpg):
In this Coulomb Explosion Imaging result, the scientists have concentrated on the hydrogen atoms (violet). Here the shape of the ring can be seen better because the hydrogen atoms are the first to be emitted from the molecule due to a charge-up of the ring-atoms. The heavier nitrogen atom is emitted later in the process, when more charge has been accumulated. Accordingly, due to larger repulsion its momentum is larger than that of the hydrogen atoms. Credit: European XFEL / Rebecca Boll, Till Jahnke

Coulomb Explosion Image of carbon and nitrogen atoms (Carbons_C.jpg):
The Coulomb Explosion Image of the molecule shows in detail the carbon atoms (red) and the nitrogen atom (green). The ring appears distorted because the detector does not register a direct image but the momentum of the fragments from the explosion, i.e., the product of their mass and velocity. The iodine atom is not displayed as it defines the horizonal axis of the momentum space coordinate system. Credit: European XFEL / Rebecca Boll, Till Jahnke

Further Information:
Professor Till Jahnke
European XFEL and 
Institute for Nuclear Physics, Goethe-University Frankfurt
Phone: + 49 (0)69-798 47023 (Secretary)
till.jahnke@xfel.eu

Rebecca Boll, Ph.D.
European XFEL
Phone: +49 (0)40 8998 6244
Phone: +49 (0)40 8994 1905
rebecca.boll@xfel.de

Editor: Dr. Markus Bernards, Science Editor, PR & Communication Office, Tel: -49 (0) 69 798-12498, Fax: +49 (0) 69 798-763 12531, bernards@em.uni-frankfurt.de