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Molecules 2018, 23(5), 1218; https://doi.org/10.3390/molecules23051218

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

1
Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians University of Munich, Butenandtstr. 5-13, 81377 Munich, Germany
2
Department of Hygiene, Microbiology and Public Health, Division of Hygiene and Medical Microbiology, Medical University Innsbruck, Schöpfstr. 41, 6020 Innsbruck, Austria
*
Author to whom correspondence should be addressed.
Academic Editors: Wenxu Zhou and De-An Guo
Received: 3 May 2018 / Revised: 15 May 2018 / Accepted: 17 May 2018 / Published: 19 May 2018
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Abstract

Mucorales are fungi with increasing importance in the clinics. Infections take a rapidly progressive course resulting in high mortality rates. The ergosterol biosynthesis pathway and sterol composition are of interest, since they are targeted by currently applied antifungal drugs. Nevertheless, Mucorales often exhibit resistance to these drugs, resulting in therapeutic failure. Here, sterol patterns of six clinically relevant Mucorales (Lichtheimia corymbifera, Lichtheimia ramosa, Mucor circinelloides, Rhizomucor pusillus, Rhizopus arrhizus, and Rhizopus microsporus) were analysed in a targeted metabolomics fashion after derivatization by gas chromatography-mass spectrometry. Additionally, the effect of posaconazole (POS) treatment on the sterol pattern of R. arrhizus was evaluated. Overall, fifteen different sterols were detected with species dependent variations in the total and relative sterol amount. Sterol analysis from R. arrhizus hyphae confronted with sublethal concentrations of posaconazole revealed the accumulation of 14-methylergosta-8,24-diene-3,6-diol, which is a toxic sterol that was previously only detected in yeasts. Sterol content and composition were further compared to the well-characterized pathogenic mold Aspergillus fumigatus. This work contributes to a better understanding of the ergosterol biosynthesis pathway of Mucorales, which is essential to improve antifungal efficacy, the identification of targets for novel drug design, and to investigate the combinatorial effects of drugs targeting this pathway. View Full-Text
Keywords: Mucorales; Rhizopus arrhizus; sterol pattern; antifungal effectivity; gas chromatography-mass spectrometry (GC-MS); posaconazole Mucorales; Rhizopus arrhizus; sterol pattern; antifungal effectivity; gas chromatography-mass spectrometry (GC-MS); posaconazole
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Müller, C.; Neugebauer, T.; Zill, P.; Lass-Flörl, C.; Bracher, F.; Binder, U. Sterol Composition of Clinically Relevant Mucorales and Changes Resulting from Posaconazole Treatment. Molecules 2018, 23, 1218.

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