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A zinc-chelating cyclic alkyl polyamine compound is efficient and safe in a murine model of multidrug-resistant Candida auris infection

Summary

Researchers tested a new drug called APC6 that works by trapping zinc, which fungi need to survive. In mouse studies of a dangerous resistant fungus called Candida auris, APC6 saved all treated mice while most untreated mice died. The drug also reduced fungal infections in organs without causing serious side effects, suggesting it could become a new treatment option for serious fungal infections resistant to current medicines.

Background

Candida auris is an emerging multidrug-resistant fungal pathogen causing severe nosocomial outbreaks with high mortality rates worldwide. Over 90% of clinical isolates are resistant to fluconazole, with increasing resistance to amphotericin B and echinocandins. Novel antifungal mechanisms targeting metal homeostasis represent a promising therapeutic strategy.

Objective

This study evaluated the in vivo efficacy and safety of APC6, a zinc-chelating cyclic alkyl polyamine compound, using a neutropenic murine model of disseminated Candida auris infection with multidrug-resistant clinical isolates from clades I and III.

Results

APC6 at 15 mg/kg achieved 100% survival in both infected cohorts compared to 50% and 25% in vehicle controls. The compound significantly reduced fungal burden in liver, kidneys, and brain (1.2-1.5 log10 CFU/g reductions). At the therapeutic dose, APC6 showed similar or superior activity to amphotericin B with no significant adverse effects and no mutagenic activity.

Conclusion

APC6 demonstrates robust in vivo efficacy against multidrug-resistant C. auris infection with a favorable safety profile, establishing zinc-chelating compounds as a viable novel antifungal class. These findings support the concept that targeting fungal metal homeostasis offers a mechanistically distinct therapeutic approach to overcome resistance to existing antifungal therapies.
  • Published in:Antimicrobial Agents and Chemotherapy,
  • Study Type:Preclinical In Vivo Study,
  • Source: 10.1128/aac.00856-25, PMID: 41004200
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