Tag Archives: Friedrich Schiller University Jena

Keanu Reeves molecule: protector of plants?

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Courtesy: Wallpaperstopick [downloaded from https://wallpaperstopick.blogspot.com/2012/05/keanu-reeves.html]

The Keanu Reeves molecule is produced by bacteria.according to a February 6, 2023 news item on phys.org,

Bacteria of the genus Pseudomonas produce a strong antimicrobial natural product, as researchers at the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI) have discovered. They proved that the substance is effective against both plant fungal diseases and human-pathogenic fungi. The study was published in the Journal of the American Chemical Society and highlighted in an editorial in Nature.

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A February 6, 2023 Leibniz Institute for Natural Product Research and Infection Biology – Hans Knoell Institute (Leibniz-HKI) press release (also on EurekAlert) by Charlotte Fuchs, which originated the news item, highlights both the published study and the special article in Nature magazine, Note: A link has been removed,

The newly discovered natural product group of keanumycins in bacteria works effectively against the plant pest Botrytis cinerea, which triggers grey mould rot and causes immense harvest losses every year. But the active ingredient also inhibits fungi that are dangerous to humans, such as Candida albicans. According to previous studies, it is harmless to plant and human cells.

Keanumycins could therefore be an environmentally friendly alternative to chemical pesticides, but they could also offer an alternative in the fight against resistant fungi. “We have a crisis in anti-infectives,” explains Sebastian Götze, first author of the study and postdoc at Leibniz-HKI. “Many human-pathogenic fungi are now resistant to antimycotics – partly because they are used in large quantities in agricultural fields.”

Deadly like Keanu Reeves

The fact that the researchers have now found a new active ingredient in bacteria of the genus Pseudomonas is no coincidence. “We have been working with pseudomonads for some time and know that many of these bacterial species are very toxic to amoebae, which feed on bacteria,” says study leader Pierre Stallforth. He is the head of the department of Paleobiotechnology at Leibniz-HKI and professor of Bioorganic Chemistry and Paleobiotechnology at Friedrich Schiller University in Jena. It appears that several toxins are responsible for the deadly effect of the bacteria, of which only one was known so far. In the genome of the bacteria, the researchers have now found biosynthesis genes for the newly discovered natural products, the keanumycins A, B and C. This group of natural products belongs to the nonribosomal lipopeptides with soap-like properties.

Together with colleagues at the Bio Pilot Plant of the Leibniz-HKI, the researchers succeeded in isolating one of the keanumycins and conducting further tests. “The lipopeptides kill so efficiently that we named them after Keanu Reeves because he, too, is extremely deadly in his roles,” Götze explains with a wink.

The researchers suspected that keanumycins could also kill fungi, as these resemble amoebas in certain characteristics. This assumption was confirmed together with the Research Centre for Horticultural Crops at the University of Applied Sciences Erfurt. There, Keanumycin was shown to be effective against grey mould rot on hydrangea leaves. In this case, culture fluid that no longer contained bacterial cells was sufficient to significantly inhibit the growth of the fungus.

“Theoretically, the keanumycin-containing supernatant from Pseudomonas cultures could be used directly for plants,” says Götze. Further testing will be carried out together with the colleagues in Erfurt. Keanumycin is biodegradable, so no permanent residues should form in the soil. This means that the natural product has the potential to become an environmentally friendly alternative to chemical pesticides.

Fungal diseases such as Botrytis cinerea, which causes grey mould rot, cause immense harvest losses in fruit and vegetable cultivation every year. More than 200 different types of fruit and vegetables are affected, especially strawberries and unripe grapes.

Possible applications in humans

“In addition, we tested the isolated substance against various fungi that infect humans. We found that it strongly inhibits the pathogenic fungus Candida albicans, among others,” says Götze.

Instead of plants, Keanumycin could therefore possibly also be used in humans. According to the tests conducted so far, the natural product is not highly toxic for human cells and is already effective against fungi in very low concentrations. This makes it a good candidate for the pharmaceutical development of new antimycotics. These are also urgently needed, as there are very few drugs against fungal infections on the market.

The work was supported by the Werner Siemens Foundation, the Leibniz Association and the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) as part of the Balance of the Microverse Cluster of Excellence, and funded by the Dr. Illing Foundation.

The study was highlighted by Nature in a “News & Views” article.

Here are citations and links to both the published study and the article in Nature,

Ecological Niche-Inspired Genome Mining Leads to the Discovery of Crop-Protecting Nonribosomal Lipopeptides Featuring a Transient Amino Acid Building Block by Sebastian Götze, Raghav Vij, Katja Burow, Nicola Thome, Lennart Urbat, Nicolas Schlosser, Sebastian Pflanze, Rita Müller, Veit G. Hänsch, Kevin Schlabach, Leila Fazlikhani, Grit Walther, Hans-Martin Dahse, Lars Regestein, Sascha Brunke, Bernhard Hube, Christian Hertweck, Philipp Franken, and Pierre Stallforth. J. Am. Chem. Soc. 2023, 145, 4, 2342–2353 DOI: https://doi.org/10.1021/jacs.2c11107 Publication Date:January 20, 2023 Copyright © 2023 The Authors. Published by American Chemical Society

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Bacterial defence repurposed to fight blight (News and Views article) by Andrew Mitchinson. Nature 614, 39 (2023) DOI: https://doi.org/10.1038/d41586-023-00195-x Published: 30 January 2023

Both the study and the ‘News and Views’ article are behind a paywall.

German scientists battle tough mucus

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A December 15, 2017 news item on ScienceDaily highlights cystic fibrosis research being done in Germany,

Around one in 3,300 children in Germany is born with Mucoviscidosis [cystic fibrosis; CF]. A characteristic of this illness is that one channel albumen on the cell surface is disturbed by mutations. Thus, the amount of water of different secretions in the body is reduced which creates a tough mucus. As a consequence, inner organs malfunction. Moreover, the mucus blocks the airways. Thus, the self regulatory function of the lung is disturbed, the mucus is colonized by bacteria and chronic infections follow. The lung is so significantly damaged that patients often die or need to have a lung transplant. The average life expectancy of a patient today is around 40 years. This is due to medical progress. Permanent treatment with inhaled antibiotics play a considerable part in this. The treatment can’t avoid the colonization by bacteria completely but it can keep it in check for a longer period of time. However, the bacteria defend themselves with a development of resistance and with the growth of so-called biofilms underneath the layer of mucus, which mostly block off the bacteria in the lower rows like a protective shield.

A complex way to the Pathogens

Scientists of the Friedrich Schiller University Jena, Germany succeeded in developing a much more efficient method to treat the airway infections which are often lethal. Crucial are nanoparticles that transport the antibiotics more efficiently to their destination….

A December 15, 2017 Friedrich Schiller University Jena press release (also on EurekAlert), which originated the news item, expands on the theme,

“Typically, the drugs are applied by inhalation in the body. Then they make a complicated way through the body to the pathogens and many of them don’t make it to their destination,” states Prof. Dr Dagmar Fischer of the chair for Pharmaceutical Technology at the University of Jena, who supervised the project together with her colleague Prof. Dr Mathias Pletz, a pulmonologist and infectious diseases physician, from the Center for Infectious Diseases and Infection Control at the Jena University Hospital. The project was supported by the Deutsche Forschungsgemeinschaft. First of all, the active particles need to have a certain size to be able to reach the deeper airways and not to bounce off somewhere else before. Ultimately, they have to penetrate the thick layer of mucus on the airways as well as the lower layers of the bacteria biofilm.

Nanoparticles travel more efficiently

To overcome the strong defense, the researchers encapsulated the active agents, like the antibiotic Tobramycin, in a polyester polymer. Thus, they created a nanoparticle which they then tested in the laboratory where they beforehand had simulated the present lung situation, in a static as well as in a dynamic state, i. e. with simulated flow movements. Therefore Pletz’s research group had developed new test systems, which are able to mimick the situation of the chronically infected CF-lung. The scientists discovered that their nanoparticle travels more easily through the sponge-like net of the mucus layer and is finally able to kill off the pathogens without any problems. Moreover, an additionally applied coating of polyethylenglycol makes it nearly invisible for the immune system. “All materials of a nanocarrier are biocompatible, biodegradable, nontoxic and therefore not dangerous for humans,” the researcher informs.

However, the Jena scientists don’t know yet exactly why their nanoparticle fights the bacteria so much more efficiently. But they want to finally get clarification in the year ahead. “We have two assumptions: Either the much more efficient transport method advances significantly larger amounts of active ingredients to the center of infection, or the nanoparticle circumvents a defense mechanism, which the bacterium has developed against the antibiotic,” the Jena Pharmacist Fischer explains. “This would mean, that we succeeded in giving back its impact to an antibiotic, which had already lost it through a development of resistance of the bacteria.”

“More specifically, we assume that bacteria from the lower layers of the biofilm transform into dormant persisters and hardly absorb any substances from outside. In this stadium, they are tolerant to most antibiotics, which only kill off self-dividing bacteria. The nanoparticles transport the antibiotics more or less against their will to the inner part of the cell, where they can unfold their impact,” Mathias Pletz adds.

Additionally, the Jena research team had to prepare the nanoparticles for the inhalation. Because at 200 nanometers the particle is too small to get into the deeper airways. “The breathing system filters out particles that are too big as well as those which are too small,” Dagmar Fischer explains. “So, we are left with a preferred window of between one and five micrometers.” The Jena researchers also have promising ideas for resolving this problem.

Coating of Nanoparticles enhances the impact of Antibiotics against Biofilms

The scientists from Jena are at this point already convinced to have found a very promising method to fight respiratory infections of patients with mucoviscidosis. Thus they may be able to contribute to a higher life expectancy of those affected. “We were able to show that the nanoparticle coating improves the impact of the antibiotics against biofilm by a factor of 1,000,” the pulmonologist and infectious diseases physician is happy to say.

It’s exciting news and I wish the researchers great success. Perhaps, one day, they will publish a paper about their work.

Sweet, sugary computer (calculator); chemistry in action

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This computer is also described as sugar-based molecular computing in a June 19, 2014 news item on Nanowerk,

In a chemistry lab at the Friedrich Schiller University Jena (Germany): Prof. Dr. Alexander Schiller works at a rectangular plastic board with 384 small wells. The chemist carefully pipets some drops of sugar solution into a row of the tiny reaction vessels. As soon as the fluid has mixed with the contents of the vessels, fluorescence starts in some of the wells. What the Junior Professor for Photonic Materials does here – with his own hands – could also be called in a very simplified way, the ‘sweetest computer in the world’. The reason: the sugar molecules Schiller uses are part of a chemical sequence for information processing.

A June 19, 2014 Friedrich Schiller University Jena news release (also on EurekAlert), which originated the news item, provides an description by the lead researcher, Schiller,

Professor Schiller explains. “There is either electricity flowing between both poles of an electric conductor or there isn’t.” These potential differences are being coded as “0” and “1” and can be linked via logic gates – the Boolean operators like AND, OR, NOT. In this way, a number of different starting signals and complex circuits are possible.

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These logic links however can also be realized with the help of chemical substances, as the Jena chemists were able to show. For their ‘sugar computer’ they use several components: One fluorescent dye and a so-called fluorescence quencher. “If there are both components involved, the colorant can’t display its impact and we don’t see a fluorescence signal,” Schiller says. But if sugar molecules are involved, the fluorescence quencher reacts with the sugar and thus loses its capability to suppress the fluorescence signal, which makes the dye fluorescent. Depending on whether the dye, the fluorescence quencher and the sugar are on hand to give the signal, a fluorescent signal results – “1” – or no signal – “0”.

“We link chemical reactions with computer algorithms in our system in order to process complex information,” Martin Elstner explains. “If a fluorescence signal is registered, the algorithm determines what goes into the reaction vessel next.” In this way signals are not translated and processed in a current flow, like in a computer but in a flow of matter. That their chemical processing platform works, Schiller and his staff demonstrated in the current study with the sample calculation 10 + 15. “It took our sugar computer about 40 minutes, but the result was correct,” Prof. Schiller says smiling, and clarifies: “It is not our aim to develop a chemical competition to established computer chips.” The chemist rather sees the field of application in medical diagnostics. So it is for instance conceivable to connect the chemical analysis of several parameters of blood and urine samples via the molecular logic platform for a final diagnosis and thus enable decisions for therapies.

Here’s a link to and a citation for the paper,

Sugar-based Molecular Computing by Material Implication by Martin Elstner, Jörg Axthelm, and Prof.Dr. Alexander Schiller. Angewandte Chemie International Edition DOI: 10.1002/anie.201403769 Article first published online: 12 JUN 2014

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

One final note, Friedrich Schiller University Jena is also known as the University of Jena.