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. 2020 Jun 18;6(2):89.
doi: 10.3390/jof6020089.

Rhizoferrin Glycosylation in Rhizopus microsporus

Anton Škríba  1 , Rutuja Hiraji Patil  1   2 , Petr Hubáček  3 , Radim Dobiáš  4 , Andrea Palyzová  1 , Helena Marešová  1 , Tomáš Pluháček  1   2 , Vladimír Havlíček  1   2
Affiliations

Rhizoferrin Glycosylation in Rhizopus microsporus

Anton Škríba et al. J Fungi (Basel). .

Abstract

Rhizopus spp. are the most common etiological agents of mucormycosis, causing over 90% mortality in disseminated infections. The diagnosis relies on histopathology, culture, and/or polymerase chain reaction. For the first time, the glycosylation of rhizoferrin (RHF) was described in a Rhizopus microsporus clinical isolate by liquid chromatography and accurate tandem mass spectrometry. The fermentation broth lyophilizate contained 345.3 ± 13.5, 1.2 ± 0.03, and 0.03 ± 0.002 mg/g of RHF, imido-RHF, and bis-imido-RHF, respectively. Despite a considerable RHF secretion rate, we did not obtain conclusive RHF detection from a patient with disseminated mucormycosis caused by the same R. microsporus strain. We hypothesize that parallel antimycotic therapy, RHF biotransformation, and metabolism compromised the analysis. On the other hand, the full profile of posaconazole metabolites was retrieved by our in house software CycloBranch.

Keywords: Rhizopus microsporus; glycoside; human isolate; liquid chromatography; mass spectrometry; metabolite; posaconazole metabolism; rhizoferrin; siderophore.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chromatographic separation and tandem mass spectrometry of R. microsporus secondary metabolites. BPC: base peak chromatogram (CASI LM or HM windows), Hex stands for hexose. (A,B), BPC in the 200–700 Daltons mass range run on fresh or aged (5 months) lyophilizates; (C–E), reconstructed ion mass chromatograms corresponding to bis-imido-RHF, imido-RHF, and RHF, respectively (0.005 Dalton window). The BPC and selected ion chromatograms of di-Hex-RHF, tetra-Hex-RHF, and di-Hex-imido-RHF are shown in panels (F–I), respectively (all HM). Panels (J–M) refer to the product ion mass spectra (10 eV collisional energy) of imido-RHF, RHF, di-Hex-RHF, and tetra-Hex-RHF, respectively. The structure on the top indicates the intrinsic fragmentation in the RHF molecule.
Figure 2
Figure 2
Annotation of posaconazole and its metabolites in the patient’s urine by CycloBranch (15 ppm accuracy, 0.4% minimum relative intensity threshold, 1,000,000 minimum absolute intensity threshold, full pattern with a minimum of three isotope peaks in at least three consecutive scans). The CycloBranch internal mucormycotic database was amended with current antifungals and their metabolites [36].
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