Browsing by Author "Sohn, Kai"

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Open Access
The 2‐methylpropene degradation pathway in Mycobacteriaceae family strains
(2023) Helbich, Steffen; Barrantes, Israel; dos Anjos Borges, Luiz Gustavo; Pieper, Dietmar H.; Vainshtein, Yevhen; Sohn, Kai; Engesser, Karl‐Heinrich
Mycolicibacterium gadium IBE100 and Mycobacterium paragordonae IBE200 are aerobic, chemoorganoheterotrophic bacteria isolated from activated sludge from a wastewater treatment plant. They use 2‐methylpropene (isobutene, 2‐MP) as the sole source of carbon and energy. Here, we postulate a degradation pathway of 2‐methylpropene derived from whole genome sequencing, differential expression analysis and peptide‐mass fingerprinting. Key genes identified are coding for a 4‐component soluble diiron monooxygenase with epoxidase activity, an epoxide hydrolase, and a 2‐hydroxyisobutyryl‐CoA mutase. In both strains, involved genes are arranged in clusters of 61.0 and 58.5 kbp, respectively, which also contain the genes coding for parts of the aerobic pathway of adenosylcobalamin synthesis. This vitamin is essential for the carbon rearrangement reaction catalysed by the mutase. These findings provide data for the identification of potential 2‐methylpropene degraders.
Open Access
Discrimination of pancreato-biliary cancer and pancreatitis patients by non-invasive liquid biopsy
(2024) Hartwig, Christina; Müller, Jan; Klett, Hagen; Kouhestani, Dina; Mittelstädt, Anke; Anthuber, Anna; David, Paul; Brunner, Maximilian; Jacobsen, Anne; Glanz, Karolina; Swierzy, Izabela; Roßdeutsch, Lotta; Klösch, Bettina; Grützmann, Robert; Wittenberger, Timo; Sohn, Kai; Weber, Georg F.
Background. Current diagnostics for the detection of pancreato-biliary cancers (PBCs) need to be optimized. We therefore propose that methylated cell-free DNA (cfDNA) derived from non-invasive liquid biopsies serves as a novel biomarker with the ability to discriminate pancreato-biliary cancers from non-cancer pancreatitis patients. Methods. Differentially methylated regions (DMRs) from plasma cfDNA between PBCs, pancreatitis and clinical control samples conditions were identified by next-generation sequencing after enrichment using methyl-binding domains and database searches to generate a discriminatory panel for a hybridization and capture assay with subsequent targeted high throughput sequencing. Results. The hybridization and capture panel, covering around 74 kb in total, was applied to sequence a cohort of 25 PBCs, 25 pancreatitis patients, 25 clinical controls, and seven cases of Intraductal Papillary Mucinous Neoplasia (IPMN). An unbiased machine learning approach identified the 50 most discriminatory methylation markers for the discrimination of PBC from pancreatitis and controls resulting in an AUROC of 0.85 and 0.88 for a training ( n = 45) and a validation ( n = 37) data set, respectively. The panel was also able to distinguish high grade from low grade IPMN samples. Conclusions. We present a proof of concept for a methylation biomarker panel with better performance and improved discriminatory power than the current clinical marker CA19-9 for the discrimination of pancreato-biliary cancers from non-cancerous pancreatitis patients and clinical controls. This workflow might be used in future diagnostics for the detection of precancerous lesions, e.g. the identification of high grade IPMNs vs. low grade IPMNs.
Open Access
Draft genome sequence of furan-degrading Rhodococcus erythropolis strain FUR100
(2024) Helbich, Steffen; Woiski, Christine; Dobslaw, Daniel; Gerl, Thomas; Vainshtein, Yevhen; Sohn, Kai; Engesser, Karl-Heinrich
Open Access
From gut to blood : spatial and temporal pathobiome dynamics during acute abdominal murine sepsis
(2023) Hartwig, Christina; Drechsler, Susanne; Vainshtein, Yevhen; Maneth, Madeline; Schmitt, Theresa; Ehling-Schulz, Monika; Osuchowski, Marcin; Sohn, Kai
Abdominal sepsis triggers the transition of microorganisms from the gut to the peritoneum and bloodstream. Unfortunately, there is a limitation of methods and biomarkers to reliably study the emergence of pathobiomes and to monitor their respective dynamics. Three-month-old CD-1 female mice underwent cecal ligation and puncture (CLP) to induce abdominal sepsis. Serial and terminal endpoint specimens were collected for fecal, peritoneal lavage, and blood samples within 72 h. Microbial species compositions were determined by NGS of (cell-free) DNA and confirmed by microbiological cultivation. As a result, CLP induced rapid and early changes of gut microbial communities, with a transition of pathogenic species into the peritoneum and blood detected at 24 h post-CLP. NGS was able to identify pathogenic species in a time course-dependent manner in individual mice using cfDNA from as few as 30 microliters of blood. Absolute levels of cfDNA from pathogens changed rapidly during acute sepsis, demonstrating its short half-life. Pathogenic species and genera in CLP mice significantly overlapped with pathobiomes from septic patients. The study demonstrated that pathobiomes serve as reservoirs following CLP for the transition of pathogens into the bloodstream. Due to its short half-life, cfDNA can serve as a precise biomarker for pathogen identification in blood.