Recent developments in the dermatophytes
The evolutionary journey of dermatophytes, the skin fungi belonging to the family Arthrodermataceae (order Onygenales), unfolds a unique pattern of adaptation to vertebrate hosts. Originating from geophilic, soil-dwelling species of Arthroderma that produce elaborate sexual fruitbodies, their evolution progressed to zoophilic association with domesticated animals. Recent shifts to the human host are accompanied by a gradual loss of sexual reproduction (Gräser et al., 2006).
The evolution of the entire family Arthrodermataceae family is estimated to span approximately 37 million years (Kandemir et al., 2021), but adaptations may have proceeded much faster since domestication of a wide variety of animals. Notably, anthropophilic dermatophytes emerge from various animal species, showcasing the human host’s unique position carrying a larger number of adapted dermatophytes than any other mammal.
The Trichophyton rubrum complex exhibits a total lack of sexual reproduction (Kosanke et al., 2018). This observation supports the hypothesis that extended human association results in emergence of divergently adapted clones, such as T. rubrum on glabrous skin and T. violaceum and T. soudanense on the scalp (Ilkit, 2010). The three asexual species demonstrate coherent differences in clinical features, morphology, physiology, and genetics, although none of these parameters is strictly diagnostic. Genetically, the entities are very similar, indicating a relatively short time of evolution. Similarly, entities have emerged in the near-absence of sexuality after sympatric evolution in the T. tonsurans complex (Kandemir et al., 2020), but due to still incomplete lineage sorting the taxa are not fully separated.
Given the longstanding clinical significance of these fungi in dermatology, we have made recommendations as to which taxa are to be reported in routine dermatology (Tang et al., 2022). The clones in T. rubrum complex cause different types of infection with 90% confidence level, and exhibit distinct colony morphology and microscopic features (Su et al., 2019). Keratin degradation and lipolysis indicate differences in ecological specialization, although such physiological tests are not practical as identification criteria. AFLP and MALDI-ToF-MS lack sufficient discriminatory power to reliably distinguish between all entities (Theel et al., 2011). Clinical manifestations remain an important criterion for identification, preferably confirmed by ITS sequencing despite the small differences between the clones. For laboratories lacking access to ITS sequencing capabilities, clinical manifestations combined with phenotypes are sufficient for identification in the T. rubrum complex. Although genetic differentiation of T. soudanense is small, its endemism in Africa as a cause of tinea capitis, combined with its phenotypic difference, makes the clinical distinction of this entity meaningful (Su et al., 2019). Differentiation is however less unambiguous within most other species complexes. The recommendation is to distinguish species of intermediate group only when a certain degree of adaptation has led to clinically relevant differences (Tang et al., 2022).
Accurate identification of etiologic agents in the T. mentagrophytes complex is still a subject of debate. The T. mentagrophytes complex encompasses 28 ITS-genotypes (Klinger et al., 2021). Švarcová et al. (2023) reported that among twelve investigated phenotypic features, statistically significant differences between clones were found only in growth rates at 37°C and in the production of spiral hyphae. Although phenotypic traits lack diagnostic value, statistically significant physiological differences among the molecular siblings suggest ongoing evolutionary trends (Tang et al., 2021). In the same T. mentagrophytes complex, correlations were observed between the clone containing the T. interdigitale type and higher patient age, as well as clinical manifestations like tinea pedis or onychomychosis. This is probably insufficient to treat T. interdigitale as a separate species. Practical distinction is also difficult due to extensive gene flow between lineages (Švarcová et al., 2023). Trichophyton mentagrophytes is recognized as the ancestral cluster of genotypes, while T. interdigitale and the recently emerging T. indotineae are prevalently anthropophilic clonal offshoots (Tang et al., 2021). Trichophyton indotineae is a significant public health concern linked to widespread antifungal misuse (Chowdhary et al., 2022; Singh et al., 2018, 2019), and is recommended for routine distinction. This approach aligns with the notion that clinical relevance reflects evolutionary significance, advocating for a nuanced understanding of molecular diversity within the T. mentagrophytes complex. The unnamed lineages within these entities may have epidemiological relevance and can be numbered as haplotypes, eliminating the need for formal taxonomic species names.
A broader perspective of evolutionary trends has been translated into a system of six genera within the Arthrodermataceae: Arthroderma, Lophophyton, Paraphyton, and the clinically relevant genera Epidermophyton, Microsporum, Trichophyton and Nannizzia (de Hoog et al., 2017). These genera are mostly morphologically distinguishable by their beautifully structured macroconidia which loose preponderance in Trichophyton. The ancestral species are carried in the fur of terrestrial mammals and produce their sexual state in the adjacent soil. Tang et al. (2023)* followed keratinolytic responses of 19 dermatophyte species using hairs of a broad range of mammals, including ancestral as well as derived species, as substrates. Zoophilic species showed more activity than anthropophilic dermatophytes, but bat hairs were remarkably difficult to degrade. It seems that evolution takes numerous sideways rather than following a single, consistent path.
Acknowledgement
*We are grateful to the veterinarians who collected hair samples from mammals: Baptiste Mulot (Beauval Zoological Park, France), Benoit Quintard (Zoological Park of Mulhouse, France), Ramona Guillot Moraru (Veterinary Clinic of Chatelet en Brie, France), Maria Dolores Sanchez, Pierre Levallois and Sabrina Vieu (Oniris, Veterinary College of Nantes, France) and Gudrun Wibbelt (Nationales Konsiliarlabor für Dermatophyten, Charité, Berlin, Germany).
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