Scientists at Imperial College London and the University of Manchester have developed a promising new way to create safer and more effective treatments for life-threatening fungal infections. The research, published today in Nature, describes a new family of antifungal agents that—when tested in mice—were more potent and less toxic than existing treatments.
Fungal diseases are an escalating global health threat, becoming harder to treat as resistance to existing drugs grows and the development of new antifungal medicines lags behind. The urgency for new treatments was emphasized by a recent report by the World Health Organization (WHO).
While existing antifungal medicines can be highly effective, many can cause serious side effects because fungal cells share similarities with human cells, making it difficult to target infections without harming healthy tissue.
Mining bacteria for new polyenes
In the new study, researchers from the Micklefield Lab focused on polyenes—a class of powerful antifungal agents. Using an approach called genome mining, they identified bacterial species capable of producing new, undiscovered antifungals.
Dr. Saadia Nasr Mirza, who worked on the project, 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."
Using a technique called nuclear magnetic resonance (NMR), the team determined the structures of the newly discovered polyenes, showing that each one had a unique structure that differed from any existing antifungal compounds. The researchers also characterized the enzymes responsible for producing them and generated a library of polyene derivatives for testing.
Several of the new compounds showed increased antifungal activity, reduced toxicity and improved solubility compared with the parent drugs. The findings demonstrate that enzymes can be used to redesign these important medicines in a cleaner, more efficient way, producing new compounds that retain strong antifungal activity while reducing toxicity and harmful side effects.
Nys34 stands out in mice
One compound, known as Nys34, showed particularly promising results. In a mouse model of invasive aspergillosis, a serious fungal infection caused by Aspergillus fumigatus, the compound reduced fungal burden without substantial signs of toxicity.
Professor Jason Micklefield, who led the project, said, "We were pleased to find that several of the new polyene derivatives were more potent and less toxic than amphotericin and nystatin, which is another important polyene that is also used in the clinic.
"Surprisingly, we found that one of the most effective new polyene derivatives, Nys34, has a different mode of action from the widely used amphotericin. Because Nys34 kills fungal cells in a different way, it could prove very useful to combat emerging pathogens that have evolved resistance to amphotericin."
A cleaner route to drug design
Polyene antifungal drugs are highly complex molecules. Previous efforts to improve them have typically relied on lengthy chemical synthesis processes that are expensive, inefficient and can require environmentally harmful reagents.
The Micklefield Lab, based at Imperial's Molecular Sciences Research Hub, developed an enzyme-based approach that can produce improved polyenes through cleaner and more efficient biological processes, generating promising new drug candidates without the need for complex multistep chemical manufacturing.
Because the process is potentially scalable and cost-effective, it could help make improved antifungal treatments more widely available, particularly in lower-income regions where fungal diseases place a substantial burden on public health.
The researchers hope that further development of Nys34 could ultimately lead to clinical testing in people. Beyond Nys34, their enzyme platform provides a powerful new way of generating and refining polyene antifungal compounds that could be used to create additional treatments for a range of fungal diseases, helping to expand the limited pipeline of new antifungal medicines.
Publication details
Jason Micklefield, Enzymatic glycosylation and amidation reshapes polyene bioactivity, Nature (2026). DOI: 10.1038/s41586-026-10834-8. www.nature.com/articles/s41586-026-10834-8
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Citation: New antimicrobials could help tackle deadly drug-resistant infections (2026, July 29) retrieved 29 July 2026 from https://phys.org/news/2026-07-antimicrobials-tackle-deadly-drug-resistant.html
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