Synthetic polymers against fungal infections
A chemistry PhD student is stranded at the Leibniz-HKI and uses the time for research on Candida albicans
When combined with antifungal drugs, synthetic polymers are particularly effective against Candida albicans. This is what a German-Australian research team found out and also clarified the mechanism of action behind it. The international collaboration came about by chance during an unplanned research stay that initiated the study at the Leibniz-HKI in Jena.
Candida albicans Hyphe (colored blue) penetrates human cells.
Ricardo Almeida/Leibniz-HKI
Every year, over two million people are affected by invasive fungal infections, which are often caused by Candida species and are associated with high mortality rates. The development of new therapies is progressing very slowly. However, the need is increasing, especially as drug resistance is developing more and more frequently. An interdisciplinary research team led by Dr. Sascha Brunke from the Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (Leibniz-HKI) has now investigated the mode of action and therapeutic potential of synthetic polymers. These long-chain chemical compounds mimic naturally occurring peptides and inhibit the growth of microorganisms. The exact mechanism of action was previously unclear. However, the mystery has now been solved - thanks to the coronavirus pandemic of all things.
From Australia to Jena
PhD student Sebastian Schäfer, who was working on the development of antifungal polymers at the University of New South Wales (UNSW) in chemical engineering, was in Germany when Australia closed its borders due to the pandemic, preventing Schäfer from returning to UNSW. But the biotechnologist made a virtue of necessity and temporarily moved his research to the Leibniz-HKI in Jena, where he added a chemical facet to the Department of Microbial Pathogenicity Mechanisms and turned his attention to pathogenic fungi. This not only led to new research approaches, but also to a very successful collaboration between natural product researchers and infection biologists from Germany and Australia.
New synthetic polymers with strong efficacy
The unexpected team developed several synthetic polymers from the polyacrylamide family that showed strong efficacy against Candida albicans , even against resistant strains. In particular, the polymer called LH, together with the drug caspofungin, was extremely effective against the fungus and significantly improved the survival rate of infected moth larvae in laboratory tests.
All-round strike against fungal cells
In the study, the team also uncovered the exact mode of action of the compounds for the first time. "The synthetic polymers attack the fungal cells in different ways at the same time. They also use new target structures and are therefore very efficient. This is the difference to conventional antimycotics, which only have a one-sided effect," reports Raghav Vij, who is one of the authors of the study alongside Sebastian Schäfer. The compounds caused stress in the fungal cell and weakened it by hindering glycosylation on the cell surface. In this chemical process, sugar chains are bound to proteins, which is important for the stability and function of the cells. The polymers also damaged the walls and membranes of the fungal cells, causing them to die. In addition, the polymers also supported immune cells in the destruction of fungal cells, as was discovered in interaction tests.
Hope for resistant fungi
"It was also remarkable that LH together with antifungal agents did not lead to the development of resistance in C. albicans in the laboratory. This indicates that such combination therapies are not only more effective, but also more sustainable than previous therapies and can therefore lead to better treatment success," explains Vij. Another plus point: "The production of synthetic polymers is relatively inexpensive. They are also stable and storable compared to conventional active ingredients. They could therefore make a significant contribution to public health, particularly in low-income countries," summarizes Sascha Brunke.
However, more research is needed before this can happen. "So far, the polymers have only been tested in insect models. Whether humans also tolerate the new therapy well must first be investigated in detail," Brunke points out. There is also still a need to optimize the structure of the polymers developed. "We don't yet know exactly which molecular components of the polymers affect which parts of the fungus. We are still missing the target molecule, so to speak," says Vij. It also needs to be tested whether the polymers have any harmful effects on humans or the environment. Despite everything, the research results already point in a positive direction and give hope for effective new treatment options.
Note: This article has been translated using a computer system without human intervention. LUMITOS offers these automatic translations to present a wider range of current news. Since this article has been translated with automatic translation, it is possible that it contains errors in vocabulary, syntax or grammar. The original article in German can be found here.
Original publication
Sebastian Schaefer, Raghav Vij, Jakob L. Sprague, Sophie Austermeier, Hue Dinh, Peter R. Judzewitsch, Sven Müller-Loennies, Taynara Lopes Silva, Eric Seemann, Britta Qualmann, Christian Hertweck, Kirstin Scherlach, Thomas Gutsmann, Amy K. Cain, Nathaniel Corrigan, Mark S. Gresnigt, Cyrille Boyer, Megan D. Lenardon, Sascha Brunke; "A synthetic peptide mimic kills Candida albicans and synergistically prevents infection"; Nature Communications, Volume 15, 2024-8-9
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