Scientists at Imperial College London and The University of Manchester announced on July 29 that they have developed a new approach to create safer and more effective treatments for life-threatening fungal infections. The research, published in Nature, introduces a family of antifungal agents that showed increased potency and reduced toxicity compared to existing treatments when tested in mice.
The team focused on polyenes, a class of powerful antifungal agents. Using genome mining, they identified bacterial species capable of producing previously undiscovered antifungals. Dr. Saadia Nasr Mirza said, "The most effective antifungal agent currently available is a polyene molecule called amphotericin produced by soil bacteria. Although amphotericin is very potent, it is highly toxic, so we set out to discover if bacteria can produce different types of polyenes that are safer than amphotericin. We developed a bioinformatics pipeline, which surprisingly showed that many bacterial species have the capability to produce novel polyenes."
Researchers used nuclear magnetic resonance (NMR) techniques to determine the structures of these newly discovered compounds and characterized the enzymes responsible for their production. This led to the creation of a library of polyene derivatives for further testing.
Several new compounds demonstrated improved antifungal activity as well as lower toxicity and better solubility compared with existing drugs. One compound, Nys34, was particularly promising; in mouse models with invasive aspergillosis caused by Aspergillus fumigatus, Nys34 reduced fungal burden without substantive signs of toxicity.
The Micklefield lab at Imperial's Molecular Sciences Research Hub developed an enzyme-based approach allowing cleaner and more efficient biological production processes for these molecules—potentially making improved treatments more accessible globally. Researchers hope further development will lead Nys34 into clinical testing and expand options for treating fungal diseases.
