Researchers at the University of Illinois at Urbana-Champaign have reimagined the antifungal drug amphotericin B, creating a safer version for patients. The findings appear in Nature, a leading scientific journal in the field.
Amphotericin B has long been a cornerstone in the fight against fungal infections because of its broad effectiveness. Yet its use is limited by toxicity risks, notably kidney damage, which means doctors reserve it for the most dire cases.
“Fungal infections pose a growing public health challenge that resembles, in terms of urgency, the surge we saw with COVID-19,” explained study leader Dr. Martin Burke. “Our goal was to take one of nature’s most potent antifungal tools and transform it into a safer, more reliable ally against fungi.”
To understand how amphotericin B works, the team studied its mechanism of action. The drug attacks fungi by removing ergosterol, a key component of fungal cell membranes. However, this mechanism can also affect the membranes of human kidney cells, where ergosterol-related cholesterol plays a protective role, leading to toxicity. This dual effect clarified why the molecule can be both life-saving against infection and harmful to host tissues.
Researchers then screened a series of amphotericin B derivatives and identified AM-2-19 as a standout candidate. AM-2-19 retained strong antifungal activity while showing improved safety for kidney tissue and reducing the likelihood of fungal resistance.
In thorough testing, AM-2-19 was evaluated against more than 500 clinically important pathogens. The compound demonstrated effectiveness against bloodstream infections and renal cell infections in both laboratory models and early human studies, underscoring its potential as a new therapeutic option.
Although additional work remains to translate these findings into widespread clinical use, the trajectory is promising. The research suggests that careful modification of existing antifungals can preserve their potency while enhancing safety, addressing a critical gap in current treatment strategies. The study’s approach also offers a framework for developing similar derivatives that balance efficacy with tolerability.
Beyond this specific compound, the investigation contributes to a broader understanding of how fungal infections develop and persist, and how host tissues respond to antifungal agents. The insights may inform future therapies that minimize organ toxicity while maintaining strong anti-fungal activity, potentially reducing hospital stays and improving outcomes for patients with severe fungal diseases.
In the broader context of antimicrobial research, these results reflect a growing emphasis on translating natural products into safer, patient-friendly medications. The work aligns with ongoing efforts to curb drug resistance and to expand the arsenal available to clinicians facing invasive fungal infections.
Experts caution that moving from laboratory success to routine clinical practice involves rigorous clinical trials, regulatory review, and careful consideration of pharmacokinetics and safety in diverse patient populations. Nevertheless, the AM-2-19 program represents a compelling step toward safer antifungal therapy that maintains effectiveness across challenging pathogens, with the potential to improve care for countless individuals affected by fungal diseases.
Previous studies in related fields have explored how fungal infections can impact the brain and other organs, highlighting the complex interplay between pathogens and host biology. The current work adds to this body of knowledge by demonstrating how targeted molecular tweaks can shift a drug’s safety profile without compromising its ability to combat fungi.