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Aetiology and Laboratory Diagnosis
Published in Raimo E Suhonen, Rodney P R Dawber, David H Ellis, Fungal Infections of the Skin, Hair and Nails, 2020
Raimo E Suhonen, Rodney P R Dawber, David H Ellis
Microsporum nanum is a zoophilic fungus frequently causing chronic non-inflammatory lesions in pigs and, rarely, causing tinea in humans; it is also present in the soil of pig-yards. Human infections are usually contracted directly from pigs or fomites. Invaded hairs typically show a sparse ectothrix or endothrix infection but do not fluoresce under Wood’s ultraviolet light. The geographical distribution is worldwide. Key features include distinctive macroconidia and culture characteristics (Figure 1.4(a) and (b)).
Novel avenues for identification of new antifungal drugs and current challenges
Published in Expert Opinion on Drug Discovery, 2022
Savarirajan et al. [63] focused on finding new antifungals in nature. They discovered that extracts from Asparagus racemosus cladodes and seeds of Cassia occidentalis have strong antifungal activity against dermatophytic fungal species, Trichophyton mentagrophytes, Trichophyton terrestre, Microsporum gypseum, and Microsporum nanum. They analyzed the extracts and partially characterized the antifungal compounds. Two compounds from C. occidentalis were described as hydroxy anthraquinones, while the active ingredient from the A. racemosus extract was a saponin. The antidermatophytic activity of the plant anthraquinones and the saponin is associated with insignificant hemolytic activity, which makes these compounds ideal for antifungal therapy. Heat shock protein 90 (Hsp90) has been shown to develop and maintain resistance to antimycotics in fungi. Thus, the use of Hsp90 as a new target provides a much needed strategy to improve the treatment of fungal diseases, as this increases the efficacy of existing antifungals and blocks the development of drug resistance. Geldanamycin, a 1,4-benzoquinone ansamycin antitumor antibiotic discovered in Streptomyces hygroscopicus [64], has been identified as one of the potential inhibitors of Hsp90 in fungal diseases. However, its anticancer activity disqualified it, so its derivatives, tanespimycin (17-N-allylamino-17-demethoxygeldanamycin, 17-AAG) and 17-N,N-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), were proposed as inhibitors of Hsp90 in fungi and dramatically increased the efficacy of fluconazole against C. albicans [65]. The search for selective Hsp90 inhibitors in fungi continues, and new compounds, e.g. SNX-2112 and CMLD-013075 with significant, up to >25-fold binding selectivity for fungal Hsp90 compared to the inhibition of Hsp90 in human cells, have recently been described [66], see Figure 1.