Abstract
The major problems in determining the causative factors of the high prevalence of dermatophytoses include the lack of a well-standardized antifungal susceptibility testing method, the low consistency of in vitro and clinical minimal inhibitory concentration values, the high genomic diversity of the population, and the unclear mechanism of pathogenicity. These factors are of particular importance when the disease is recalcitrant and relapses. Herein, we identified and characterized Trichophyton mentagrophytes isolates obtained from therapy-resistant cases in humans and animals. We used genomic diversity analysis of 17 human and 27 animal clinical isolates with the MP-PCR technique, determined their phenotypic enzymatic activity and host range, and performed antifungal susceptibility testing to currently available antifungal drugs from various chemical groups. Genomic diversity values of 35.3% and 33.3% were obtained for clinical isolates from humans and animals, respectively, yet without any relationship to the host species or antifungal drug to which resistance in therapy was revealed. The highest activity of keratinase enzymes was recorded for fox, guinea pig, and human hairs. These hosts can be considered as the main species in the host range of these isolates. A phenyl morpholine derivative, i.e. amorolfine, exhibited superior activity against strains obtained from both humans and animals with the lowest MIC50. Interestingly, high compliance of terbinafine in vitro resistance with clinical problems in the treatment with this substance was shown as well. The high resistance of dermatophytes to drugs is the main cause of the recalcitrance of the infection, whereas the other features of the fungus are less important.
Highlights
Dermatophytes are the most commonly encountered fungi in humans and other vertebrates spreading through direct or indirect contacts with infected individuals and soil [1, 2]
Trichophyton mentagrophytes ATCC4439 and T. rubrum ATCC4438 served as quality controls for every new series of Minimum inhibitory concentrations (MICs) plates
Given the growing prevalence of superficial dermatophyte infections, especially in immunocompromised patients, these diseases are regarded as a public health issue worldwide [8]
Summary
Dermatophytes are the most commonly encountered fungi in humans and other vertebrates spreading through direct or indirect contacts with infected individuals and soil [1, 2]. Many studies of the mechanism of the pathogenicity of dermatophytes have been carried out over the years, there have been no concrete proposals whether it is possible to construct a profile of animal hosts susceptible to individual species of dermatophytes [22,23,24,25] In this context, it is difficult to clearly determine whether the growing prevalence of dermatophytoses is caused only by changes observed in the natural environment and lifestyles or by increased host sensitivity, a higher degree of dermatophyte pathogenicity, or the weakness of the currently available antifungal arsenal [18, 19, 22, 26]
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