# Synergistic Antifungal Activity of Zinc Pyrithione and Nystatin against Multi-Drug-Resistant Candida (Candidozyma) auris: Evidence from In Vitro and In Vivo Models

## TL;DR

A combination of zinc pyrithione and nystatin shows strong antifungal effects against drug-resistant Candida auris in lab and animal tests.

## Contribution

The study introduces a synergistic antifungal combination of ZnPT and NYS against multi-drug-resistant C. auris.

## Key findings

- ZnPT + NYS combination effectively inhibits C. auris biofilm formation and increases membrane permeability.
- The combination showed low genotoxic risk and remained within safe limits in toxicity tests.
- ZnPT alone was toxic to Tenebrio molitor larvae, but the combination was safer.

## Abstract

Candida (Candidozyma) auris is
a multidrug-resistant fungal pathogen that presents a growing global
health concern due to its resistance to conventional antifungals.
This study evaluated the antifungal potential of zinc pyrithione (ZnPT)
and nystatin (NYS), both individually and in combination, against C. auris. Minimum inhibitory and fungicidal concentrations
were determined, alongside assays for biofilm inhibition and eradication,
including tests on porcine skin. Mechanistic evaluations included
assessments of cell membrane integrity, efflux pump inhibition, and
sorbitol protection. Safety was analyzed through hemocompatibility,
the Ames test, and acute toxicity in Tenebrio molitor larvae. ZnPT + NYS combination had a synergistic antifungal effect,
effectively inhibiting biofilm formation and increasing membrane permeability,
as evidenced by protein leakage. No nucleotide leakage or mutagenic
effects were observed, indicating low genotoxic risk. While ZnPT alone
exhibited toxicity in T. molitor, the combination
remained within safe limits. Overall, the ZnPT + NYS combination demonstrated
strong antifungal and antibiofilm activity against C. auris, with favorable safety outcomes. These findings support further
investigation into its clinical potential as a treatment strategy
against this emerging pathogen.