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PhD candidate Xueke Niu investigated major trends of evolution of resistance to different azole drugs in the fungi. The research group, led by Sybren de Hoog and Paul Verweij from Medical Microbiology, in collaboration with Michaela Lackner from the Medical University of Innsbruck, published the results in the ASM journal Microbiology Spectrum.
Antifungal drug resistance is an increasing problem in modern medicine, which extends far beyond MRSA. Especially the rapid emergence of multi-drug resistant yeast such as Candida auris and the Covid-19-associated Mucorales have challenged patient care and hospital hygiene. Minimum Inhibitory Concentration (MIC) data provide a guideline to clinical treatment. MIC data of the infections fungal species have been widely published and a meta-analysis was performed in the course of the study. Different visualization plots were used to organize and classify the huge data set, to show where resistance seems to be intrinsic, and where it is acquired e.g. under the pressure of agricultural azole use, as known for Aspergillus fumigatus. It was found that several clinically relevant groups, among which Histoplasma and related systemic pathogens, the dermatophytes and the black yeasts, are naturally susceptible to azoles, with occasional emergence of acquired resistance due to specific mutations. However, large fungal groups show high degrees of azole multi-resistance, and hence are difficult to treat. This is the case with the entire orders of Hypocreales and Microascales (Fusarium, Scedosporium and relatives) and the Mucorales (Rhizopus), while also the mushrooms and shelf fungi exhibit decreased susceptibility. Natural resistance versus susceptibility was strongly associated with phylogenetic distances, members of the same order mostly showing similar behaviour. 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. Main traits of antifungal resistance were plotted on a phylogenetic tree of the fungal Kingdom, clearly showing high degrees of natural resistance being consistent at the ordinal level. This provides a framework for further studies on fungus-drug interactions.
Publication
Niu X, Al-Hatmi AMS, Vitale RG, Lackner M, Ahmed SA, Verweij PE, Kang Y, de Hoog S. Evolutionary trends in antifungal resistance: a meta-analysis. Microbiol Spectr. 2024 Apr 2;12(4):e0212723. doi: 10.1128/spectrum.02127-23. Epub 2024 Mar 6. PMID: 38445857.
Fungal infections tend to be recalcitrant, with frequent relapse, and hence management is problematic in immunocompromised patients and sometimes even in otherwise healthy individuals.
