According to research from the University of Illinois Urbana-Champaign and partners at the University of Wisconsin-Madison, a novel antifungal molecule created by modifying the structure of well-known antifungal drug Amphotericin B has the potential to maximize the drug's effectiveness against fungal infections while eliminating its toxicity. This research is published in the journal Nature.
Amphotericin B is a medication used as a last option to treat fungal infections. It is a naturally occurring tiny chemical manufactured by bacteria. Although AmB is highly effective in eliminating fungus, it should only be used as a last resort due to its toxicity to humans, especially to the kidneys.
"The public health catastrophe of fungal diseases is only get worse. Regretfully, they possess the capability to emerge and have a massive influence, comparable to that of COVID-19. Thus, let us transform one of the potent instruments that nature created to fight fungus into a potent ally "study leader Dr. Martin D. Burke, a chemistry professor at the University of Illinois, a professor at the Carle Illinois College of Medicine, and a physician.
"This work is a demonstration that, by going deep into the fundamental science, you can take a billion-year head start from nature and turn it into something that hopefully is going to have a big impact on human health," Burke stated.
Burke's team has been studying AmB for years in an effort to create a derivative that will destroy fungus without endangering people. In earlier research, they collaborated with a team led by professor Chad Rienstra of the University of Wisconsin-Madison that specialized in solid-state nuclear magnetic resonance, a molecular imaging technique, and created and utilized a building block-based method to chemical synthesis. Together, the scientists discovered the drug's mechanism of action: AmB acts like a sponge to draw ergosterol from fungal cells, killing the fungus.
Burke and Rienstra's groups collaborated once more on the latest study, which discovered that AmB also causes kidney cell death in humans by removing cholesterol, the most prevalent sterol. Additionally, the atomic-level structure of AmB sponges linked to cholesterol and ergosterol was determined by the researchers.
"The atomic resolution models were really the key to zoom in and identify these very subtle differences in binding interactions between AmB and each of these sterols," said Corinne Soutar, a graduate student from Illinois and one of the paper's collaborators.
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