Sterol Composition of Clinically Relevant Mucorales and Changes Resulting from Posaconazole Treatment.

作者: Christoph Müller , Thomas Neugebauer , Patrizia Zill , Cornelia Lass-Flörl , Franz Bracher

DOI: 10.3390/MOLECULES23051218

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摘要: Mucorales are fungi with increasing importance in the clinics. Infections take a rapidly progressive course resulting high mortality rates. The ergosterol biosynthesis pathway and sterol composition of interest, since they targeted by currently applied antifungal drugs. Nevertheless, often exhibit resistance to these drugs, therapeutic failure. Here, patterns six clinically relevant (Lichtheimia corymbifera, Lichtheimia ramosa, Mucor circinelloides, Rhizomucor pusillus, Rhizopus arrhizus, microsporus) were analysed metabolomics fashion after derivatization gas chromatography-mass spectrometry. Additionally, effect posaconazole (POS) treatment on pattern R. arrhizus was evaluated. Overall, fifteen different sterols detected species dependent variations total relative amount. Sterol analysis from hyphae confronted sublethal concentrations revealed accumulation 14-methylergosta-8,24-diene-3,6-diol, which is toxic that previously only yeasts. content further compared well-characterized pathogenic mold Aspergillus fumigatus. This work contributes better understanding Mucorales, essential improve efficacy, identification targets for novel drug design, investigate combinatorial effects drugs targeting this pathway.

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