Antifungal resistance in the fungal Kingdom
Antifungal drug resistance is an increasing problem in the clinic. Especially the rapid emergence of multi-drug resistant yeasts such as Candida auris and the severe Covid-19-associated mucoralean infections have challenged patient care and hospital hygiene. Since recently, a multi-drug-resistant dermatophyte, Trichophyton indotineae, is rapidly spreading over the globe (Jabet et al. 2022).
Most studies on antifungals focus on the acquired arm of resistance, i.e. the growing number of strains within fungal populations over a particular time period (Fisher et al. 2022), usually under the pressure of environmental conditions such as agricultural azole use (Macedo et al. 2019) or inappropriate application of creams by the public (Singh et al. 2019). This is well-known for Aspergillus fumigatus, and seems to be dependent on particular environmental conditions (Verweij et al. 2020). Several other clinically relevant groups, such as Histoplasma and related dimorphic pathogens, the dermatophytes, and the black yeasts, are susceptible to azoles and show no sign of resistant adaptation (de Hoog et al. 2020).
Other fungi are naturally resistant to most commonly used antifungals, independent from This phenomenon is not scattered through the fungal Kingdom. Natural resistance versus susceptibility is strongly associated with phylogeny, members of the same order mostly showing similar behaviour. This was clearly shown by Niu et al. (2024) using data available in the Atlas of Clinical Fungi. Intrinsic resistance is characteristic for all members of the orders of Hypocreales and Microascales (Fusarium, Trichoderma, Scedosporium, Scopulariopsis and relatives) and the Mucorales (Mucor, Rhizopus), while also the mushrooms and shelf fungi exhibit decreased susceptibility. This implies that phylogeny broadly predicts antifungal resistance. In the yeasts, phylogenetic distances are very large, and thus it seems that Candida auris is an exceptional, resistant maverick in Candida, but actually its related species also show high degrees of resistance. Niu et al. (2024) plotted main traits of antifungal resistance on a phylogenetic tree of the fungal Kingdom, and showed high degrees of natural resistance in several orders. This provides an important framework for further studies on fungus-drug interactions. Infections by resistant fungi tend to be recalcitrant, with frequent relapse, and hence management is problematic in immunocompromised patients and sometimes even in otherwise healthy individuals.
A one-day course on dermatophytes and some other Onygenales, which includes presentations on Trichophyton indotineae, will be organized as a pre-congress activity of the International Mycological Congress in Maastricht, The Netherlands, 11-15 August, 2024 https://imc12.org/.
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