UK scientists develop less toxic antifungals, Nature reports
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Scientists at Imperial College London and the University of Manchester have developed a new class of polyene antifungal agents that are more effective and less toxic than existing drugs, according to a study published Wednesday in Nature. One compound, Nys34, reduced fungal burden in mice with invasive aspergillosis without substantial side effects. The findings come as the World Health Organization warns of a growing threat from drug-resistant fungal infections.
Genome Mining and Redesign
The research team, led by Professor Jason Micklefield at Imperial College London, used a bioinformatics pipeline to identify bacterial species capable of producing novel polyene antifungals. They discovered that many bacteria have the genetic machinery for unique polyene structures, which were then analyzed via nuclear magnetic resonance (NMR). The scientists also characterized the enzymes involved in polyene synthesis, enabling the creation of a library of derivatives with improved properties.
Efficacy in Mouse Model
Among the derivatives, Nys34 stood out in tests on mice infected with Aspergillus fumigatus, the cause of invasive aspergillosis. Nys34 reduced fungal burden without significant toxicity, outperforming the current frontline drugs amphotericin B and nystatin in both potency and safety. Several other derivatives also showed increased solubility and antifungal activity, suggesting a broad platform for drug development. The study, published in Nature, demonstrates that enzyme-mediated redesign can yield safer polyenes.
What's Next
The researchers plan to conduct further preclinical studies to assess Nys34's safety profile and efficacy against a wider range of fungal pathogens. It remains uncertain when or if these compounds will progress to human clinical trials, given the high failure rate in antifungal drug development.
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UK scientists develop less toxic antifungals, Nature reports
