When combined with antifungal drugs, synthetic polymers are particularly effective against the yeast Candida albicans. This is what a German-Australian research team found out and also clarified the mechanism of action behind it. The researchers presented their findings in the journal "Nature Communications". The study was carried out as part of the Cluster of Excellence "Balance of the Microverse" External link at the University of Jena and was funded by the German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF), among others.
High demand for therapies against fungal infections
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 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.
All-round strike against fungal cells
The research team developed several synthetic polymers from the polyacrylamide family that showed strong efficacy against Candida albicans , even against resistant strains. The polymer called LH in particular, together with the drug caspofungin, was extremely effective against the fungus and significantly improved the survival rate of infected moth larvae in laboratory tests.
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. The compounds cause stress in the fungal cell and weaken 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 determined in interaction tests.
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, the researchers concluded.
