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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Glabonjat, RA; Kitsera, M; Unterhauser, K; Lembacher-Fadum, C; Högenauer, C; Raber, G; Breinbauer, R; Zechner, EL.
Simultaneous quantification of enterotoxins tilimycin and tilivalline in biological matrices using HPLC high resolution ESMS² based on isotopically ¹⁵N-labeled internal standards.
Talanta. 2021; 222(1):121677-121677 Doi: 10.1016/j.talanta.2020.121677 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Co-Autor*innen der Med Uni Graz: Hoegenauer Christoph
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Abstract:: Non-ribosomal peptides are one class of bacterial metabolites formed by gut microbiota. Intestinal resident Klebsiella oxytoca produces two pyrrolobenzodiazepines, tilivalline and tilimycin, via the same nonribosomal biosynthesis platform. These molecules cause human disease by genotoxic and tubulin inhibitory activities resulting in apoptosis of the intestinal epithelium, loss of barrier integrity and ultimately colitis. Here we report a fast, reliable, HPLC-HR-ESMS² method for quantifying simultaneously the bacterial enterotoxins tilimycin and tilivalline in complex biological matrices. We synthesized and applied stable isotopically labeled internal standards for precise quantification of the metabolites. Sample preparation was optimized using clinical and laboratory specimens including serum, colonic fluid and stool. The developed method overcame the disadvantage of low selectivity by applying high resolution mass spectrometry in MS² mode. High sensitivity and low interference from matrices were achieved and validated. We show that the approach is suitable for detection and quantification of the enterotoxic metabolites produced in vivo, in infected human or animal hosts, and in bacterial culture in vitro. Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
Find related publications in this database (Keywords): Bacterial metabolites; Pyrrolobenzodiazepines; Non-ribosomal peptides; High performance liquid chromatography; High-resolution mass spectrometry; MS/MS; Stable isotope dilution; Intestinal disease