Modulation of ERG gene expression in fluconazole-resistant human and animal isolates of Trichophyton verrucosum

Abstract

Dermatophytes are a group of eukaryotic microorganisms characterized by high capacity to colonize keratinized structures such as the skin, hair, and nails. Over the past years, the incidence of infections caused by zoophilic species, e.g., Trichophyton verrucosum, has been increasing in some parts of the world, especially in Europe. Moreover, the emergence of recalcitrant dermatophytoses and in vitro resistant dermatophytes has become a cause of concern worldwide. Here, we analyzed the mechanisms underlying resistance to fluconazole among clinical isolates of T. verrucosum. Quantitative RT-PCR was carried out to determine the relative expression levels of mRNA transcripts of ERG3, ERG6, and ERG11 genes in the fungal samples using the housekeeping gene GAPDH as a reference. Our results showed that the upregulation of the ERG gene expression is a possible mechanism of resistance to fluconazole in this species. Furthermore, ERG11 is the most statistically significantly overexpressed gene in the pool of fluconazole-resistant T. verrucosum isolates. Additionally, we have demonstrated that exposure to fluconazole increases the levels of expression of ERG genes in fluconazole-resistant isolates of T. verrucosum. In conclusion, this study has shown one of the possible mechanisms of resistance to fluconazole among zoophilic dermatophytes, which involves the maintenance of high levels of expression of ERG genes after drug exposure.

Molecular study and antifungal susceptibility profile of Trichophyton rubrum and Trichophyton mentagrophytes strains isolated from lesions of humans and cattle

“…The study of the relationship between the frequency of pathogenic genes and resistance to antifungal drugs showed that strains with polymorphic ERG genes were resistant to drugs, while strains without this gene family were sensitive to all antifungals (p<0.01). This association can be attributed to the mechanism of the polymorphic ERG gene in counteracting antifungal drugs ( 28 ). Ergosterol is a major component of yeast cell membrane sterols and is also responsible for maintaining cell function and integrity.…”