Abstract
Onychomycosis is mainly caused by two dermatophyte species, Trichophyton rubrum and Trichophyton interdigitale. A study of nail invasion mechanisms revealed that the secreted subtilisin Sub6, which has never been detected under in vitro growth conditions, was the main protease secreted by T. rubrum and T. interdigitale during infection. In contrast, most of the proteases secreted during the digestion of keratin in vitro were not detected in infected nails. The hypothesis that proteases isolated from dermatophytes grown in a keratin medium are virulence factors is no longer supported. Non-dermatophyte fungi can also be infectious agents in nails. It is necessary to identify the infectious fungus in onychomycosis to prescribe adequate treatment, as moulds such as Fusarium spp. and Aspergillus spp. are insensitive to standard treatments with terbinafine or itraconazole, which are usually applied for dermatophytes. In these refractory cases, topical amphotericin B treatment has shown to be effective. Terbinafine treatment failure against dermatophytes is also possible, and is usually due to resistance caused by a missense mutation in the squalene epoxidase enzyme targeted by the drug. Trichophyton resistance to terbinafine treatment is an emerging problem, and a switch to azole-based treatment may be necessary to cure such cases of onychomycosis.
Highlights
Two species of dermatophyte, Trichophyton rubrum and Trichophyton interdigitale, are the cause of most onychomycosis, often following fungal infection of the interdigital or plantar spaces [1]
Aspergillus spp. are insensitive to standard treatments with terbinafine or itraconazole, which are usually applied for dermatophytes
Introduction of the detected point mutations into terbinafine-sensitive T. mentagrophytes generated terbinafine-resistant phenotypes for which the terbinafine MIC was comparable to that of corresponding clinical strains [39]. These results showed that terbinafine resistance in Trichophyton clinical isolates had to be imputed to the detected amino acid substitution in the squalene epoxidase (SQLE) protein
Summary
Trichophyton rubrum and Trichophyton interdigitale, are the cause of most onychomycosis, often following fungal infection of the interdigital or plantar spaces [1]. The infectious agents of nail infections are dermatophytes and moulds and yeasts of the genus Candida. The diagnosis of onychomycosis is usually primarily based on the detection of a fungus in nail samples by direct mycological examination, on the isolation and identification of the infectious fungus in culture [1]. The purpose of this article is to briefly review recent findings on fungal nail infection and to present new perspectives for improving their treatment.
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