New Approach to Combat Fungal Infections Discovered by Researchers
Researchers at the RIKEN Center for Sustainable Research Science (CSRS) and the University of Toronto have made a breakthrough in the fight against fungal infections. In a recent study published in the journal Cell Chemical Biology, the researchers revealed a new way to attack fungal infections by blocking fungi from being able to produce fatty acids, the major component of fats.
Fungal infections have become a growing concern worldwide, with diseases caused by the Candida, Cryptococcus, and Aspergillus types of fungi resulting in millions of deaths each year. Similar to bacterial resistance to antibiotics, fungal resistance to medications is also increasing. Currently, there are only three major classes of anti-fungal medications that work by destroying the barrier around fungal cells. However, these treatments are specific to certain species and may not be effective against a broad range of fungi.
The researchers aimed to find an alternative approach that would be effective against numerous species of harmful fungi. They screened a natural product depository called RIKEN NPDepo against four pathogenic yeasts, including three Candida species and one Cryptococcus species. The screening identified several compounds that significantly reduced fungal growth in each of the four species.
After eliminating compounds that were already known, the researchers were left with three new possibilities. Among the three, the compound named NPD6433 was found to be the least toxic to human cells and also reduced the growth of Aspergillus fumigatus, a common and deadly fungal mold.
Further investigation revealed that NPD6433 likely works by inhibiting fatty acid synthase, an enzyme involved in fatty acid production. By preventing the production of fatty acids inside fungal cells, NPD6433 and another fatty acid synthase inhibitor called cerulenin were able to kill numerous yeast species in laboratory culture.
To test the effectiveness of NPD6433 in a live organism, the researchers conducted experiments using the worm Caenorhabditis elegans, which was infected with a pathogenic yeast. Treating the infected worms with NPD6433 resulted in a significant reduction in fatalities, even in cases where the yeast was resistant to standard anti-fungal medications.
The lead author of the study, Yoko Yashiroda from RIKEN CSRS, expressed optimism about the findings, stating, “Our research indicates that targeting fatty acid synthesis is a promising alternative therapeutic strategy for fungal infections, and one which might not require tailor-made solutions for individual species.”
This new approach to combating fungal infections offers hope in the battle against drug-resistant fungi. The discovery of compounds like NPD6433 paves the way for the development of new drugs that can effectively target a broad range of fungal species.