TY  - JOUR
A1  - López, Cristina
A1  - Kleinheinz, Kortine
A1  - Aukema, Sietse M.
A1  - Rohde, Marius
A1  - Bernhart, Stephan H.
A1  - Hübschmann, Daniel
A1  - Wagener, Rabea
A1  - Toprak, Umut H.
A1  - Raimondi, Francesco
A1  - Kreuz, Markus
A1  - Waszak, Sebastian M.
A1  - Huang, Zhiqin
A1  - Sieverling, Lina
A1  - Paramasivam, Nagarajan
A1  - Seufert, Julian
A1  - Sungalee, Stephanie
A1  - Russell, Robert B.
A1  - Bausinger, Julia
A1  - Kretzmer, Helene
A1  - Ammerpohl, Ole
A1  - Bergmann, Anke K.
A1  - Binder, Hans
A1  - Borkhardt, Arndt
A1  - Brors, Benedikt
A1  - Claviez, Alexander
A1  - Doose, Gero
A1  - Feuerbach, Lars
A1  - Haake, Andrea
A1  - Hansmann, Martin-Leo
A1  - Hoell, Jessica
A1  - Hummel, Michael
A1  - Korbel, Jan O.
A1  - Lawerenz, Chris
A1  - Lenze, Dido
A1  - Radlwimmer, Bernhard
A1  - Richter, Julia
A1  - Rosenstiel, Philip
A1  - Rosenwald, Andreas
A1  - Schilhabel, Markus B.
A1  - Stein, Harald
A1  - Stilgenbauer, Stephan
A1  - Stadler, Peter F.
A1  - Szczepanowski, Monika
A1  - Weniger, Marc A.
A1  - Zapatka, Marc
A1  - Eils, Roland
A1  - Lichter, Peter
A1  - Loeffler, Markus
A1  - Möller, Peter
A1  - Trümper, Lorenz
A1  - Klapper, Wolfram
A1  - Hoffmann, Steve
A1  - Küppers, Ralf
A1  - Burkhardt, Birgit
A1  - Schlesner, Matthias
A1  - Siebert, Reiner
T1  - Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma
JF  - Nature Communications
N2  - Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing.
KW  - cancer genomics
KW  - lymphocytes
KW  - lymphoid tissues
KW  - oncology
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-237281
VL  - 10
ER  - 
TY  - JOUR
A1  - Hennessen, Fabienne
A1  - Miethke, Marcus
A1  - Zaburannyi, Nestor
A1  - Loose, Maria
A1  - Lukežič, Tadeja
A1  - Bernecker, Steffen
A1  - Hüttel, Stephan
A1  - Jansen, Rolf
A1  - Schmiedel, Judith
A1  - Fritzenwanker, Moritz
A1  - Imirzalioglu, Can
A1  - Vogel, Jörg
A1  - Westermann, Alexander J.
A1  - Hesterkamp, Thomas
A1  - Stadler, Marc
A1  - Wagenlehner, Florian
A1  - Petković, Hrvoje
A1  - Herrmann, Jennifer
A1  - Müller, Rolf
T1  - Amidochelocardin overcomes resistance mechanisms exerted on tetracyclines and natural chelocardin
JF  - Antibiotics
N2  - The reassessment of known but neglected natural compounds is a vital strategy for providing novel lead structures urgently needed to overcome antimicrobial resistance. Scaffolds with resistance-breaking properties represent the most promising candidates for a successful translation into future therapeutics. Our study focuses on chelocardin, a member of the atypical tetracyclines, and its bioengineered derivative amidochelocardin, both showing broad-spectrum antibacterial activity within the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) panel. Further lead development of chelocardins requires extensive biological and chemical profiling to achieve favorable pharmaceutical properties and efficacy. This study shows that both molecules possess resistance-breaking properties enabling the escape from most common tetracycline resistance mechanisms. Further, we show that these compounds are potent candidates for treatment of urinary tract infections due to their in vitro activity against a large panel of multidrug-resistant uropathogenic clinical isolates. In addition, the mechanism of resistance to natural chelocardin was identified as relying on efflux processes, both in the chelocardin producer Amycolatopsis sulphurea and in the pathogen Klebsiella pneumoniae. Resistance development in Klebsiella led primarily to mutations in ramR, causing increased expression of the acrAB-tolC efflux pump. Most importantly, amidochelocardin overcomes this resistance mechanism, revealing not only the improved activity profile but also superior resistance-breaking properties of this novel antibacterial compound.
KW  - chelocardins
KW  - atypical tetracyclines
KW  - broad-spectrum antibiotics
KW  - clinical isolates
KW  - uropathogens
KW  - urinary tract infection (UTI)
KW  - resistance-breaking properties
KW  - mechanism of resistance
KW  - AcrAB-TolC efflux pump
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-213149
SN  - 2079-6382
VL  - 9
IS  - 9
ER  -