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Bartonella bacteria use certain proteins – conserved pathomechanism in other bacterial species
Researchers from University Hospital Frankfurt and Goethe University Frankfurt have unravelled how bacteria adhere to host cells and thus taken the first step towards developing a new class of antibiotics.
FRANKFURT. The adhesion of bacteria to host cells is always the first and one of the decisivesteps in the development of infectious diseases. The purpose of this adhesion by infectious pathogens is first to colonize the host organism (i.e., the human body), and then to trigger an infection, which in the worst case can end fatally. Precise understanding of the bacteria's adhesion to host cells is a key to finding therapeutic alternatives that block this critical interaction in the earliest possible stage of an infection.
Critical interaction with the human protein fibronectin
In collaboration with other researchers, scientists from University Hospital Frankfurt and Goethe University Frankfurt have now explained the exact bacterial adhesion mechanism using the human-pathogenic bacterium Bartonella henselae. This pathogen causes “cat-scratch disease", a disease transmitted from animals to humans. In an international collaborative project led by the Frankfurt research group headed by Professor Volkhard Kempf, the bacterial adhesion mechanism was deciphered with the help of a combination of in-vitro adhesion tests and high-throughput proteomics. Proteomics is the study of all the proteins present in a cell or a complex organism.
The scientists have shed light on a key mechanism: the bacterial adhesion to the host cells can be traced back to the interaction of a certain class of adhesins – called “trimeric autotransporter adhesins" – with fibronectin, a protein often found in human tissue. Adhesins are components on the surface of bacteria which enable the pathogen to adhere to the host's biological structures. Homologues of the adhesin identified here as critical are also present in many other human-pathogenic bacteria, such as the multi-resistant Acinetobacter baumannii, which the World Health Organization (WHO) has classified as the top priority for research into new antibiotics.
State-of-the-art protein analytics were used to visualize the exact points of interaction between the proteins. In addition, it was possible to show that experimental blocking of these processes almost entirely prevents bacterial adhesion. Therapeutic approaches that aim to prevent bacterial adhesion in this way could represent a promising treatment alternative as a new class of antibiotics (known as “anti-ligands") in the constantly growing domain of multi-resistant bacteria.
The research work was funded as part of an Innovative Training Network (“ViBrANT: Viral and Bacterial Adhesin Network Training") under the Marie Skłodowska-Curie Actions (MSCA) of the European Union's HORIZON 2020 research and innovation programme.
The scientific paper has been published in
the prestigious journal “Microbiology Spectrum" of the American Society of
Microbiology (ASM) and was acknowledged as “Paper of the Month" by the German
Society for Hygiene and Microbiology (DGHM) on 18 June 2022.
Publication: Vaca, D. J., Thibau, A., Leisegang, M. S., Malmström, J., Linke, D., Eble, J. A., Ballhorn, W., Schaller, M., Happonen, L., Kempf, V. A. J.; Interaction of Bartonella henselae with Fibronectin Represents the Molecular Basis for Adhesion to Host Cells; Microbiology Spectrum, 18 April, 2022. https://doi.org/10.1128/spectrum.00598-22
https://www.kgu.de/fileadmin/redakteure/Presse/Bilder_Pressmitteilungen/2022/Vaca_Diana_Jaqueline.jpgCaption: First author of the study: Diana Jaqueline Vaca, Institute of Medical Microbiology and Hospital Hygiene at University Hospital Frankfurt. Photo: University Hospital Frankfurt
Adhesion of Bartonella henselae (blue) to human blood vessel cells (red). The bacterium's adhesion to the host cells could be blocked with the help of what are known as “anti-ligands".
Professor Volkhard A. J. Kempf
Director of the Institute of Medical Microbiology and Hospital Hygiene
University Hospital Frankfurt
Tel.: +49 (0)69 6301–5019
Editor: Christoph Lunkenheimer, Press Officer, Staff Unit Communication at Universitätsklinikum Frankfurt, Phone: +49 (0)69 6301–86442, firstname.lastname@example.org
German-American research team deciphers evolution of pathogenic Acinetobacter strains
Hospital-acquired infections (HAIs) are often particularly difficult to treat because the pathogens have developed resistance to common antibiotics. The bacterium Acinetobacter baumannii is particularly dreaded in this respect, and research is seeking new therapeutic approaches to combat it. To look for suitable starting points, an international team led by bioinformaticians at Goethe University Frankfurt has compared thousands of genomes of pathogenic and harmless Acinetobacter strains. This has delivered clues about which properties might have made A. baumannii a successful pathogen – and how it might possibly be combated.
FRANKFURT/ST. LOUIS. Each year, over 670,000 people in Europe fall ill through pathogenic bacteria that exhibit antibiotic resistance, and 33,000 die of the diseases they cause. Especially feared are pathogens that are resistant to several antibiotics at the same time. Among them is the bacterium Acinetobacter baumannii, which is today dreaded above all as a “hospital superbug": up to five percent of all hospital-acquired bacterial infections are caused by this germ alone.
A. baumannii is right at the top of a list of candidates for which, according to the World Health Organization (WHO), new therapies must be developed. This is because the pathogen – due to a flexible genome – easily acquires new antibiotic resistance. At the same time, infections are not only occurring more and more outside the hospital environment but also leading to increasingly severe progression. However, a prerequisite for the development of new therapeutic approaches is that we understand which properties make A. baumannii and its human pathogenic relatives, grouped in what is known as the Acinetobacter calcoaceticus-baumannii (ACB) complex, a pathogen.
A team led by bioinformatician Professor Ingo Ebersberger from Goethe University Frankfurt/ LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG) has now reached a milestone in this understanding. The team is composed of members of Research Unit 2251 of the German Research Foundation and other national and international partners, among them scientists of Washington University School of Medicine, St Louis, USA.
For their analysis, the team made use of the fact that a large proportion of the members of the Acinetobacter genus are harmless environmental bacteria that live in water or on plants or animals. Thousands of complete genome sequences both of these as well as of pathogenic Acinetobacter strains are stored in publicly accessible databases.
By comparing these genomes, the researchers were able to systematically filter out differences between the pathogenic and the harmless bacteria. Because the incidence of individual genes was not particularly conclusive, Ebersberger and his colleagues concentrated on gene clusters, that is, groups of neighbouring genes that have remained stable during evolution and might form a functional unit. “Of these evolutionarily stable gene clusters, we identified 150 that are present in pathogenic Acinetobacter strains and rare or absent in their non-pathogenic relatives," says Ebersberger, summing up. “It is highly probable that these gene clusters benefit the pathogens' survival in the human host."
Among the most important properties of pathogens is their ability to form protective biofilms and to efficiently absorb micronutrients such as iron and zinc. And indeed, the researchers discovered that the uptake systems in the ACB group were a reinforcement of the existing and evolutionary older uptake mechanism.
Particularly exciting is the fact that the pathogens have evidently tapped a special source of energy: they can break down the carbohydrate kynurenine produced by humans, which as a messenger substance regulates the innate immune system. The bacteria apparently kill two birds with one stone in this way. On the one hand, breaking down kynurenine supplies them with energy, and on the other hand, they could possibly use it to deregulate the host's immune response.
Ebersberger is convinced: “Our work is a milestone in understanding what's different about pathogenic Acinetobacter baumannii. Our data are of such a high resolution that we can even look at the situation in individual strains. This knowledge can now be used to develop specific therapies against which, with all probability, resistance does not yet exist."
Publication: Bardya Djahanschiri, Gisela Di Venanzio, Jesus S. Distel, Jennifer Breisch, Marius Alfred Dieckmann, Alexander Goesmann, Beate Averhoff, Stephan Göttig, Gottfried Wilharm, Mario F. Feldman, Ingo Ebersberger: Evolutionarily stable gene clusters shed light on the common grounds of pathogenicity in the Acinetobacter calcoaceticus-baumannii complex. PLOS Genetics (2022) DOI: 10.1371/journal.pgen.1010020 https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1010020
Scanning electron micrograph of a cluster of Gram-negative, immobile bacteria of the Acinetobacter baumannii species. Photo: Janice Carr
Professor Ingo Ebersberger
Institute of Cell Biology and Neuroscience
Goethe University Frankfurt
Tel.: +49 69 798 42112
Goethe University Frankfurt’s Science Magazine, Forschung Frankfurt, on the topic of motion has now been published in English – New Priority Programme focuses on facial and manual gestures
Communication consists not only of spoken words and phrases. We also convey important information by gesturing with our arms, hands and face. Visual communication, a field so far scarcely studied by theoretical linguistics, is the focus of a new Priority Programme of the German Research Foundation coordinated by Goethe University Frankfurt. Read more in the current issue of “Forschung Frankfurt" entitled “In motion".
FRANKFURT. How gestures and facial expressions can underline, supplement and modify the meaning of words and phrases is something that several disciplines at Goethe University Frankfurt are exploring. Linguistics professor Cornelia Ebert is interested in how the contribution of the meaning of gestures can be modelled. Until recently, visual contributions to meaning were not dealt with in formal linguistics, but instead first and foremost in communication sciences as well as in rhetoric, semiotics and psychology.
Together with Professor Markus Steinbach, sign language researcher at the University of Göttingen, Ebert has successfully applied for a Priority Programme of the German Research Foundation and is responsible for its coordination. The objective is to bring together existing findings from various disciplines and link them with linguistics. You can read about the research questions that the programme will address in the latest issue of Forschung Frankfurt, the Science Magazine of Goethe University Frankfurt, which is dedicated to the topic of motion.
In other articles, scientists from Goethe University Frankfurt report on their research projects related to various aspects of motion, for example how they teach computers to recognise different movements such as “cutting" or “waving", how ADHD can affect adults too or how two movements in quantum physics are superimposed, each of which only occurs with a certain probability. Other articles explore, for example, how smartphones, which are almost ubiquitous, are changing film as a medium or how sports clubs can foster the integration of immigrants.
Journalists can order the current English-language issue of Forschung Frankfurt (2/2021) free of charge from: email@example.com
All articles are available online at
www.forschung-frankfurt.de (then go to EN)
Editor: Dr Markus Bernards, Science Editor, PR & Communication Office, Tel: -49 (0) 69 798-12498, Fax: +49 (0) 69 798-763 12531, firstname.lastname@example.org
Bi-directional binding and release of hydrogen in bioreactor
A team of microbiologists from Goethe University Frankfurt has succeeded in using bacteria for the controlled storage and release of hydrogen. This is an important step in the search for carbon-neutral energy sources in the interest of climate protection. The corresponding paper has now been published in the renowned scientific journal “Joule".
FRANKFURT. The fight against climate change is making the search for carbon-neutral energy sources increasingly urgent. Green hydrogen, which is produced from water with the help of renewable energies such as wind or solar power, is one of the solutions on which hopes are pinned. However, transporting and storing the highly explosive gas is difficult, and researchers worldwide are looking for chemical and biological solutions. A team of microbiologists from Goethe University Frankfurt has found an enzyme in bacteria that live in the absence of air and bind hydrogen directly to CO2, in this way producing formic acid. The process is completely reversible – a basic requirement for hydrogen storage. These acetogenic bacteria, which are found, for example, in the deep sea, feed on carbon dioxide, which they metabolise to formic acid with the aid of hydrogen. Normally, however, this formic acid is just an intermediate product of their metabolism and further digested into acetic acid and ethanol. But the team led by Professor Volker Müller, head of the Department of Molecular Microbiology and Bioenergetics, has adapted the bacteria in such a way that it is possible not only to stop this process at the formic acid stage but also to reverse it. The basic principle has already been patented since 2013.
“The measured rates of CO2 reduction to formic acid and back are the highest ever measured and many times greater than with other biological or chemical catalysts; in addition, and unlike chemical catalysts, the bacteria do not require rare metals or extreme conditions for the reaction, such as high temperatures and high pressures, but instead do the job at 30 °C and normal pressure," reports Müller. The group now has a new success to report: the development of a biobattery for hydrogen storage with the help of the same bacteria.
For municipal or domestic hydrogen storage, a system is desirable where the bacteria first store hydrogen and then release it again in one and the same bioreactor and as stably as possible over a long period of time. Fabian Schwarz, who wrote his doctoral thesis on this topic at Professor Müller's laboratory, has succeeded in developing such a bioreactor. He fed the bacteria hydrogen for eight hours and then put them on a hydrogen diet during a 16-hour phase overnight. The bacteria then released all the hydrogen again. It was possible to eliminate the unwanted formation of acetic acid with the help of genetic engineering processes. “The system ran extremely stably for at least two weeks," explains Fabian Schwarz, who is pleased that this work has been accepted for publication in “Joule", a prestigious journal for chemical and physical process engineering. “That biologists publish in this important journal is somewhat unusual," says Schwarz.
Volker Müller had already studied the
properties of these special bacteria in his doctoral thesis – and spent many years
conducting fundamental research on them. “I was interested in how these first
organisms organised their life processes and how they managed to grow in the absence
of air with simple gases such as hydrogen and carbon dioxide," he explains. As
a result of climate change, his research has acquired a new, application-oriented
dimension. Surprisingly for many engineers, biology can produce by all means practicable
solutions, he says.
Publication: Fabian M. Schwarz, Florian Oswald, Jimyung Moon, Volker Müller: Biological hydrogen storage and release through multiple cycles of bi-directional hydrogenation of CO2 to formic acid in a single process unit. Joule (2022) https://doi.org/10.1016/j.joule.2022.04.020
Picture download: https://www.uni-frankfurt.de/119545783
Caption: Model of a potential bacterial hydrogen storage system: during the day, electricity is generated with the help of a photovoltaic unit, which then powers the hydrolysis of water. The bacteria bind the hydrogen produced in this way to CO2, resulting in the formation of formic acid. This reaction is fully reversible, and the direction of the reaction is steered solely by the concentration of the starting materials and end products. During the night, the hydrogen concentration in the bioreactor decreases and the bacteria begin to release the hydrogen from the formic acid again. This hydrogen can then be used as an energy source.
Professor Volker Müller
Department of Molecular Microbiology & Bioenergetics
Institute for Molecular Biosciences
Goethe University Frankfurt
Tel.: +49 (0)69 798-29507
Editor: Dr. Anke Sauter, Science Editor, PR & Communication Office, Tel. +49 69 798-13066, Fax + 49 69 798-763-12531, email@example.com
Team from Goethe University contributes to article in “Nature”
Atmospheric researchers from the international CLOUD consortium have discovered a mechanism that allows nuclei for ice clouds to form and rapidly grow in the upper troposphere. The discovery is based on cloud chamber experiments to which a team from Goethe University contributed highly specialised measurements. Although the conditions for nucleus formation are only fulfilled in the Asian monsoon region, the mechanism is expected to have an impact on ice cloud formationacross large parts of the Northern Hemisphere (Nature DOI 10.1038/s41586-022-04605-4)
FRANKFURT. The Asian monsoon transports enormous amounts of air from atmospheric layers close to Earth's surface to a height of around 15 kilometres. Like in a gigantic elevator, human-induced pollutants also end up in the upper troposphere in this way. A research team from the CLOUD consortium (Cosmics Leaving Outdoor Droplets), including atmospheric researchers from Goethe University in Frankfurt, have reproduced the conditions prevailing there, among them cosmic radiation, in their experimental chamber at the CERN particle accelerator centre in Geneva.
In the process, they identified that up to 100 times more aerosol particles form from ammonia, nitric acid and sulphuric acid than when only two of these substances are present. These particles are then available on the one hand as condensation nuclei for liquid water droplets in clouds and on the other hand as solid seeds for pure ice clouds, so-called cirrus clouds. The research team also observed that ice clouds with the three-component particles already form at lower water vapour supersaturation than anticipated. This means that the ice clouds already develop under conditions that atmospheric researchers worldwide had so far assumed did not lead to the formation of cirrus clouds. With model calculations from around the globe, the CLOUD research team was also able to show that the cloud nuclei can spread across large parts of the Northern Hemisphere within just a few days.
“The experiment in the cloud chamber was a reaction to the results of field experimentsover Asia. These measurements showed that ammonia is present there in the upper troposphere during the monsoon," explains Professor Joachim Curtius from Goethe University. “Previously, we had always assumed that ammonia, due to its water solubility, was rinsed out of the rising air masses before it reached the upper troposphere." As the CLOUD researchers' experiment now corroborates, ammonia is an essential ingredient for more cloud formation. Ammonia emissions in Asia come predominantly from agriculture.
The international CLOUD research collaboration (Cosmics Leaving Outdoor Droplets) is made up of teams from 21 research institutions. In the experiment of which the research team is now presenting the results in the current issue of “Nature", the researchers led by Curtius were responsible for the mass spectrometric measurement of the sulphuric acid concentration. This concentration changed over the course of the experiment, but was still always very low, like in the upper troposphere: for a single sulphuric acid molecule there are over a trillion other gas molecules. “Apart from the very best measuring equipment, such measurements require highly specialised expertise. That is why you need teams with complementary skills to conduct such an experiment," explains Curtius, who is a member of the CLOUD steering committee and was coordinator of the EU project CLOUD-MOTION successfully completed just recently. Like in the atmosphere, sulphuric acid forms in the CLOUD chamber from sulphur dioxide and hydroxyl radicals.
Clouds are an important and at the same time still insufficiently understood element of global climate. Depending on whether they float high up or low down, their water or ice content, how thick they are or over which region of the globe they form, it gets warmer or colder beneath them. To improve the precision of climate models, researchers worldwide require exact knowledge of all the processes surrounding clouds as a climate factor. The CLOUD research team's findings are helping them a long way towards increasingly reliable climate predictions.
Publication: Mingyi Wang et al., Synergistic HNO3 H2SO4 NH3 upper tropospheric particle formation. Nature https://www.nature.com/articles/s41586-022-04605-4, DOI 10.1038/s41586-022-04605-4
Caption: Air pollutants form the condensation nuclei for ice clouds or cirrus clouds (here: Cirrus spissatus). When ammonia, nitric acid and sulfuric acid are present together, they form such condensation nuclei particularly effectively. Credit: Joachim Curtius, Goethe-University Frankfurt
Professor Joachim Curtius
Institute for Atmospheric and Environmental Sciences
Goethe University, Frankfurt, Germany
Phone +49 (0)69 798-40258