Dermatophytosis is a fungal infection of skin, hair and nails, and the most frequently found causative agent is Trichophyton rubrum. The disease is very common and often recurring, and it is therefore difficult to eradicate. To develop and test novel treatments, infection models that are representative of the infection process are desirable. Several infection models have been developed, including the use of cultured cells, isolated corneocytes, explanted human skin, or reconstituted human epidermis. However, these have various disadvantages, ranging from not being an accurate reflection of the site of infection, as is the case with e.g. cultured cells, to being difficult to scale up or having ethical issues (e.g. explanted human skin). We therefore sought to develop an infection model using explanted porcine skin, which is low cost and ethically neutral. We show that in our model, fungal growth is dependent on the presence of skin, and adherence of conidia is time-dependent with maximum adherence observed after ~2 hours. Scanning electron microscopy suggested the production of fibril-like material that links conidia to each other and to skin. Prolonged incubation of infected skin leads to luxurious growth and invasion of the dermis, which is not surprising as the skin is not maintained in conditions to keep the tissue alive, and therefore is likely to lack an active immune system that would limit fungal growth. Therefore, the model developed seems useful to study the early stages of infection. Furthermore, we demonstrate that the model can be used to test novel treatment regimens for tinea infections.

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Dermatophytosis is a fungal infection of skin, nails and hair. Treatments can be long and infections are often recurrent, and novel treatments are desirable. Here we tested the use of polymeric films that can be sprayed on the skin for the prevention and treatment of dermatophytosis. The two polymers selected were ABIL T Quat 60 and Eudragit E100, which were tested ex vivo using a porcine skin model, and in vitro using microbiological and microscopy techniques. Acceptability of the polymeric films was tested on the skin of healthy volunteers. The results showed that ABIL and Eudragit films prevented and treated fungal skin infections. Whilst polymer films may provide a physical barrier that prevents fungal colonization, it was shown that both polymers are active antifungals ex vivo and in vitro and have intrinsic antifungal activity. For ABIL, we also established that this polymer binds essential nutrients such as metal ions and sugars, thereby restricting the growth of fungi. When applied to healthy subjects’ skin, the polymeric films neither modified the skin color nor increased trans-epidermal water loss, suggesting a low potential for skin irritation, and the approach was generally found to be acceptable for use by the volunteers. In conclusion, we developed a novel strategy for the potential prevention and treatment of dermatophytosis.

Background Superficial fungal infections are one of the most common causes of human disease caused by dermatophytes or yeasts. Dermatophyte infections are caused by fungi that can digest keratin, infecting the keratinised tissues e.g. skin, hair and nails. It has a higher prevalence than the other superficial mycoses, and its incidence has increased continuously over the last few decades, probably because of the change in lifestyle and frequent usage of antibiotics. Therefore, the aim of the project is to develop a physical barrier that can prevent the early stages of infection to the skin, to avoid development of antifungal resistance and cross-contamination. Materials/methods We developed an ex vivo model using porcine skin to study the potential of film-forming agents in prevention and treatment of dermatophytosis caused by Trichophyton rubrum. We used cell viability assays, confocal and electron microscopy to study the effects of film-forming agents on T. rubrum, followed by using QTOF-LCMS and NMR to analyse the carbohydrates binding and chelation to study its mechanism of action. Results A cationic polymer used in pharmaceutical and cosmetic products inhibited growth of T. rubrum on porcine skin. Viability assays indicated that the polymer has a fungistatic activity and microscopy imaging indicated it formed a coating on top of T. rubrum. The QTOF-LCMS and NMR indicated the polymer inhibits fungal growth by removing the carbohydrate content and chelation. Conclusions The present study suggests this cationic polymer has considerable antifungal activity against Trichophyton rubrum by preventing the supply of nutrients to the fungi.