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Publications in peer reviewed journals
Viruses comprise an extensive pool of mobile genetic elements in eukaryote cell cultures and human clinical samples.2017 - FASEB J., in press
Viruses shape a diversity of ecosystems by modulating their microbial, eukaryotic, or plant host metabolism. The complexity of virus-host interaction networks is progressively fathomed by novel metagenomic approaches. By using a novel metagenomic method, we explored the virome in mammalian cell cultures and clinical samples to identify an extensive pool of mobile genetic elements in all of these ecosystems. Despite aseptic treatment, cell cultures harbored extensive and diverse phage populations with a high abundance of as yet unknown and uncharacterized viruses (viral dark matter). Unknown phages also predominated in the oropharynx and urine of healthy individuals and patients infected with cytomegalovirus despite demonstration of active cytomegalovirus replication. The novelty of viral sequences correlated primarily with the individual evaluated, whereas relative abundance of encoded protein functions was associated with the ecologic niches probed. Together, these observations demonstrate the extensive presence of viral dark matter in human and artificial ecosystems.-Thannesberger, J., Hellinger, H.-J., Klymiuk, I., Kastner, M.-T., Rieder, F. J. J., Schneider, M., Fister, S., Lion, T., Kosulin, K., Laengle, J., Bergmann, M., Rattei, T., Steininger, C. Viruses comprise an extensive pool of mobile genetic elements in eukaryote cell cultures and human clinical samples.
Lifestyle and Horizontal Gene Transfer-Mediated Evolution of Mucispirillum schaedleri, a Core Member of the Murine Gut Microbiota.2017 - mSystems, 1: in press
Mucispirillum schaedleri is an abundant inhabitant of the intestinal mucus layer of rodents and other animals and has been suggested to be a pathobiont, a commensal that plays a role in disease. In order to gain insights into its lifestyle, we analyzed the genome and transcriptome of M. schaedleri ASF 457 and performed physiological experiments to test traits predicted by its genome. Although described as a mucus inhabitant, M. schaedleri has limited capacity for degrading host-derived mucosal glycans and other complex polysaccharides. Additionally, M. schaedleri reduces nitrate and expresses systems for scavenging oxygen and reactive oxygen species in vivo, which may account for its localization close to the mucosal tissue and expansion during inflammation. Also of note, M. schaedleri harbors a type VI secretion system and putative effector proteins and can modify gene expression in mucosal tissue, suggesting intimate interactions with its host and a possible role in inflammation. The M. schaedleri genome has been shaped by extensive horizontal gene transfer, primarily from intestinal Epsilon- and Deltaproteobacteria, indicating that horizontal gene transfer has played a key role in defining its niche in the gut ecosystem. IMPORTANCE Shifts in gut microbiota composition have been associated with intestinal inflammation, but it remains unclear whether inflammation-associated bacteria are commensal or detrimental to their host. Here, we studied the lifestyle of the gut bacterium Mucispirillum schaedleri, which is associated with inflammation in widely used mouse models. We found that M. schaedleri has specialized systems to handle oxidative stress during inflammation. Additionally, it expresses secretion systems and effector proteins and can modify the mucosal gene expression of its host. This suggests that M. schaedleri undergoes intimate interactions with its host and may play a role in inflammation. The insights presented here aid our understanding of how commensal gut bacteria may be involved in altering susceptibility to disease.
Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide.2017 - Sci Rep, 41002
Characterisation of G protein-coupled receptors (GPCR) relies on the availability of a toolbox of ligands that selectively modulate different functional states of the receptors. To uncover such molecules, we explored a unique strategy for ligand discovery that takes advantage of the evolutionary conservation of the 600-million-year-old oxytocin/vasopressin signalling system. We isolated the insect oxytocin/vasopressin orthologue inotocin from the black garden ant (Lasius niger), identified and cloned its cognate receptor and determined its pharmacological properties on the insect and human oxytocin/vasopressin receptors. Subsequently, we identified a functional dichotomy: inotocin activated the insect inotocin and the human vasopressin V1b receptors, but inhibited the human V1aR. Replacement of Arg8 of inotocin by D-Arg8 led to a potent, stable and competitive V1aR-antagonist ([D-Arg8]-inotocin) with a 3,000-fold binding selectivity for the human V1aR over the other three subtypes, OTR, V1bR and V2R. The Arg8/D-Arg8 ligand-pair was further investigated to gain novel insights into the oxytocin/vasopressin peptide-receptor interaction, which led to the identification of key residues of the receptors that are important for ligand functionality and selectivity. These observations could play an important role for development of oxytocin/vasopressin receptor modulators that would enable clear distinction of the physiological and pathological responses of the individual receptor subtypes.
Unraveling the microbial processes of black band disease in corals through integrated genomics.2017 - Sci Rep, 40455
Coral disease outbreaks contribute to the ongoing degradation of reef ecosystems, however, microbial mechanisms underlying the onset and progression of most coral diseases are poorly understood. Black band disease (BBD) manifests as a cyanobacterial-dominated microbial mat that destroys coral tissues as it rapidly spreads over coral colonies. To elucidate BBD pathogenesis, we apply a comparative metagenomic and metatranscriptomic approach to identify taxonomic and functional changes within microbial lesions during in-situ development of BBD from a comparatively benign stage termed cyanobacterial patches. Results suggest that photosynthetic CO2-fixation in Cyanobacteria substantially enhances productivity of organic matter within the lesion during disease development. Photosynthates appear to subsequently promote sulfide-production by Deltaproteobacteria, facilitating the major virulence factor of BBD. Interestingly, our metagenome-enabled transcriptomic analysis reveals that BBD-associated cyanobacteria have a putative mechanism that enables them to adapt to higher levels of hydrogen sulfide within lesions, underpinning the pivotal roles of the dominant cyanobacterium within the polymicrobial lesions during the onset of BBD. The current study presents sequence-based evidence derived from whole microbial communities that unravel the mechanism of development and progression of BBD.
PGSB/MIPS PlantsDB Database Framework for the Integration and Analysis of Plant Genome Data.2017 - Methods Mol. Biol., 33-44
Plant Genome and Systems Biology (PGSB), formerly Munich Institute for Protein Sequences (MIPS) PlantsDB, is a database framework for the integration and analysis of plant genome data, developed and maintained for more than a decade now. Major components of that framework are genome databases and analysis resources focusing on individual (reference) genomes providing flexible and intuitive access to data. Another main focus is the integration of genomes from both model and crop plants to form a scaffold for comparative genomics, assisted by specialized tools such as the CrowsNest viewer to explore conserved gene order (synteny). Data exchange and integrated search functionality with/over many plant genome databases is provided within the transPLANT project.