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

Sebastian Gnat,Dominik Łagowski,Aneta Nowakiewicz,Mariusz Dyląg,Aneta Ptaszyńska

doi:10.1007/s42770-021-00585-1

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.

Highlights

Dermatophytes are a group of primarily pathogenic filamentous fungi classified in the Arthrodermataceae family, within the order Onygenales [1]
Based on the quantitative reverse transcription PCR, different levels of expression of the ERG3, ERG6, and ERG11 genes were shown in the pool of the clinical isolates of T. verrucosum
The exposure to fluconazole induced a higher level of ERG3, ERG6, and ERG11 gene expression in the cells of the resistant isolates compared to the sensitive ones (Fig. 2)

Summary

Introduction

Dermatophytes are a group of primarily pathogenic filamentous fungi classified in the Arthrodermataceae family, within the order Onygenales [1]. These eukaryotic microorganisms are characterized by a high capacity to attack keratinized structures such as the skin, hair, and nails in humans and animals causing mainly superficial cutaneous infections [2]. Most of the literature data indicate the occurrence of infections caused by these species of dermatophytes in animals, zoonoses of these etiologies have been reported in humans professionally involved in animal husbandry [9, 12, 13]. The reverse zoonosis caused by T. verrucosum has been reported in Europe [8]

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Conclusion