Population differentiation, antifungal susceptibility, and host range of Trichophyton mentagrophytes isolates causing recalcitrant infections in humans and animals

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.

Therapeutic efficacy of topically used luliconazole vs. terbinafine 1% creams

“…Zoophilic origin dermatophytosis, primarily caused by T. mentagrophytes, is a troublesome cutaneous disease spreading worldwide with an increasing incidence. 3,7,30 Furthermore, complete cure is not easily achievable with the currently available antifungal therapy. 3,9 One of the proposed causes of treatment unresponsiveness is antifungal resistance; however, other factors may be responsible for treatment failure, since the number of recalcitrant cases exceeds the number of resistant isolates.…”

“…For example, improper hygiene, occlusive footwear, socioeconomic conditions, new types of professions, animal breeding in flats, frequent trips to warm climate regions, civilisation diseases such as diabetes mellitus, increasing resistance of pathogens to antifungal substances and even climate change have been attributed to this notable increase in the prevalence of fungal infections. [3][4][5][6][7][8] In recent years, the introduction of new antifungal agents has provided major advances in the therapy of dermatophytosis. 3,8,9 One of such drugs, luliconazole, was first approved for therapy in Japan in 2005.Later, it was approved in India and the United States in 2010 and 2013, respectively.…”

Real-Time PCR as an Alternative Technique for Detection of Dermatophytes in Cattle Herds

“…The enzymatic activities were evaluated using specific test media, as previously described [27,30]. Briefly, dermatophytes were cultured on Sabouraud's glucose agar (Becton Dickinson, NJ, USA) and incubated at 37 • C for seven days.…”

“…Technologically advanced methods of dermatophyte identification developed recently include molecular methods based on PCR [25,26]. Moreover, real-time PCR techniques are increasingly frequently used in the diagnosis of human dermatomycoses, due to their high specificity and sensitivity in the detection of dermatophytes directly from clinical samples, and even if cultures assessed with conventional methods are negative [22,25,27]. These qPCR methods have so far only occasionally been used in veterinary mycology.…”

A global view on fungal infections in humans and animals: opportunistic infections and microsporidioses

“…Nonetheless, fungal infections are relatively uncommon diseases in healthy and immunocompetent humans and animals compared with bacterial and viral infections, even though fungal infectious propagules are present in the environment in great numbers, making contacts with them inevitable (Köhler et al, 2015;Gnat et al, 2020a). On the other hand, although their prevalence is low, a growing tendency of recalcitrant and recurrent fungal infectious diseases caused by true and opportunistic pathogens has been noticed worldwide over the last decades in both humans and animals (Fisher et al, 2012;Bishnoi et al, 2018;Shenoy and Jayaraman, 2019;Gnat et al, 2020c).…”