Iranian Biomedical Journal

Iranian Biomedical Journal

Effect of Cold Atmospheric Plasma on Hsp90 Gene Expression in Terbinafine-Resistant Fungal Strains of the Trichophyton mentagrophytes Complex

Authors
Ameneh Shajari 1
Zahra Salehi 2
Mohammad Atyabi 3
1 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
2 Department of Mycology, Pasteur Institute of Iran, Tehran, Iran
3 Department of Nano Biotechnology, Pasteur Institute of Iran, Tehran, Iran
Abstract
Introduction: The Trichophyton mentagrophytes complex, particularly terbinafine-resistant fungal strains, has emerged as a major cause of chronic and recurrent dermatophytosis, which is increasingly difficult to treat. These dermatophytes cause persistent infections of the skin, and nails, often accompanied by inflammation, severe itching, keratin degradation, and reduced quality of life. In fungi, the molecular chaperone Hsp90 is essential for stress tolerance, morphogenesis, and antifungal resistance. Cold atmospheric plasma (CAP), a non-thermal ionized gas, has recently gained attention for its notable antifungal activity. This study investigates the effect of CAP on Hsp90 gene expression in terbinafine-resistant isolates of the T. mentagrophytes complex.

Materials and Methods: Fifty isolates of the T. mentagrophytes complex were tested for terbinafine susceptibility using broth microdilution, following the CLSI M38-A2 protocol. Isolates with minimum inhibitory concentrations above 0.25 µg/mL were classified as resistant. These resistant isolates, along with a standard sensitive strain (PFCC 5809), were exposed to a helium-based CAP jet, which was applied directly to fungal suspensions in 96-well microtitier plates. The expression levels of Hsp90 before and after CAP exposure were quantified by real-time PCR using ΔΔCt method.

Results and Discussion: The baseline expression of Hsp90 was 124.7-fold higher in resistant isolates compared to the sensitive strain. CAP treatment reduced Hsp90 expression to 13.3-fold, which was significantly lower than baseline levels (p < 0.005).

Conclusion: CAP significantly downregulated Hsp90 expression in terbinafine-resistant fungal strains. These findings suggest that CAP may serve as a promising adjunct antifungal strategy to enhance the management of resistant dermatophytosis.

Keywords
Antifungal therapy
Cold atmospheric plasma
Hsp90
Terbinafine resistance
Trichophyton mentagrophytes