TY - JOUR A1 - Klughammer, Johanna A1 - Dittrich, Marcus A1 - Blom, Jochen A1 - Mitesser, Vera A1 - Vogel, Ulrich A1 - Frosch, Matthias A1 - Goesmann, Alexander A1 - Müller, Tobias A1 - Schoen, Christoph T1 - Comparative genome sequencing reveals within-host genetic changes in Neisseria meningitidis during invasive disease JF - PLoS ONE N2 - Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation. In line with the hypothesis that phase variation evolved as an adaptation to colonize diverse hosts, computational comparisons of all 27 to date completely sequenced and annotated meningococcal genomes retrieved from public databases showed that contingency genes are indeed enriched for genes involved in host interactions. To assess within-host genetic changes in meningococci, we further used ultra-deep whole-genome sequencing of throat-blood strain pairs isolated from four patients suffering from invasive meningococcal disease. We detected up to three mutations per strain pair, affecting predominantly contingency genes involved in type IV pilus biogenesis. However, there was not a single (set) of mutation(s) that could invariably be found in all four pairs of strains. Phenotypic assays further showed that these genetic changes were generally not associated with increased serum resistance, higher fitness in human blood ex vivo or differences in the interaction with human epithelial and endothelial cells in vitro. In conclusion, we hypothesize that virulence of meningococci results from accidental emergence of invasive variants during carriage and without within host evolution of invasive phenotypes during disease progression in vivo. KW - blood KW - comparative genomics KW - throat KW - genetic loci KW - Neisseria meningitidis KW - genomic libraries KW - genome sequencing KW - sequence assembly tools Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159547 VL - 12 IS - 1 ER - TY - JOUR A1 - Mende, Daniel R. A1 - Letunic, Ivica A1 - Huerta-Cepas, Jaime A1 - Li, Simone S. A1 - Forslund, Kristoffer A1 - Sunagawa, Shinichi A1 - Bork, Peer T1 - proGenomes: a resource for consistent functional and taxonomic annotations of prokaryotic genomes JF - Nucleic Acids Research N2 - The availability of microbial genomes has opened many new avenues of research within microbiology. This has been driven primarily by comparative genomics approaches, which rely on accurate and consistent characterization of genomic sequences. It is nevertheless difficult to obtain consistent taxonomic and integrated functional annotations for defined prokaryotic clades. Thus, we developed proGenomes, a resource that provides user-friendly access to currently 25 038 high-quality genomes whose sequences and consistent annotations can be retrieved individually or by taxonomic clade. These genomes are assigned to 5306 consistent and accurate taxonomic species clusters based on previously established methodology. proGenomes also contains functional information for almost 80 million protein-coding genes, including a comprehensive set of general annotations and more focused annotations for carbohydrate-active enzymes and antibiotic resistance genes. Additionally, broad habitat information is provided for many genomes. All genomes and associated information can be downloaded by user-selected clade or multiple habitat-specific sets of representative genomes. We expect that the availability of high-quality genomes with comprehensive functional annotations will promote advances in clinical microbial genomics, functional evolution and other subfields of microbiology. proGenomes is available at http://progenomes.embl.de. KW - biology KW - genomic sequence KW - prokaryotic clade KW - proGenomes KW - habitat information KW - taxonomic description KW - genome collection KW - comparative genomics KW - genomics research Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171987 VL - 45 IS - D1 ER - TY - JOUR A1 - Schartl, Manfred A1 - Kneitz, Susanne A1 - Volkoff, Helene A1 - Adolfi, Mateus A1 - Schmidt, Cornelia A1 - Fischer, Petra A1 - Minx, Patrick A1 - Tomlinson, Chad A1 - Meyer, Axel A1 - Warren, Wesley C. T1 - The piranha genome provides molecular insight associated to its unique feeding behavior JF - Genome Biology and Evolution N2 - The piranha enjoys notoriety due to its infamous predatory behavior but much is still not understood about its evolutionary origins and the underlying molecular mechanisms for its unusual feeding biology. We sequenced and assembled the red-bellied piranha (Pygocentrus nattereri) genome to aid future phenotypic and genetic investigations. The assembled draft genome is similar to other related fishes in repeat composition and gene count. Our evaluation of genes under positive selection suggests candidates for adaptations of piranhas’ feeding behavior in neural functions, behavior, and regulation of energy metabolism. In the fasted brain, we find genes differentially expressed that are involved in lipid metabolism and appetite regulation as well as genes that may control the aggression/boldness behavior of hungry piranhas. Our first analysis of the piranha genome offers new insight and resources for the study of piranha biology and for feeding motivation and starvation in other organisms. KW - whole-genome sequencing KW - genome annotation KW - comparative genomics KW - RNA-seq transcriptome KW - energy homeostasis Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202218 VL - 11 IS - 8 ER - TY - JOUR A1 - Biju, Joseph A1 - Schwarz, Roland A1 - Linke, Burkhard A1 - Blom, Jochen A1 - Becker, Anke A1 - Claus, Heike A1 - Goesmann, Alexander A1 - Frosch, Matthias A1 - Müller, Tobias A1 - Vogel, Ulrich A1 - Schoen, Christoph T1 - Virulence Evolution of the Human Pathogen Neisseria meningitidis by Recombination in the Core and Accessory Genome JF - PLoS One N2 - Background Neisseria meningitidis is a naturally transformable, facultative pathogen colonizing the human nasopharynx. Here, we analyze on a genome-wide level the impact of recombination on gene-complement diversity and virulence evolution in N. meningitidis. We combined comparative genome hybridization using microarrays (mCGH) and multilocus sequence typing (MLST) of 29 meningococcal isolates with computational comparison of a subset of seven meningococcal genome sequences. Principal Findings We found that lateral gene transfer of minimal mobile elements as well as prophages are major forces shaping meningococcal population structure. Extensive gene content comparison revealed novel associations of virulence with genetic elements besides the recently discovered meningococcal disease associated (MDA) island. In particular, we identified an association of virulence with a recently described canonical genomic island termed IHT-E and a differential distribution of genes encoding RTX toxin- and two-partner secretion systems among hyperinvasive and non-hyperinvasive lineages. By computationally screening also the core genome for signs of recombination, we provided evidence that about 40% of the meningococcal core genes are affected by recombination primarily within metabolic genes as well as genes involved in DNA replication and repair. By comparison with the results of previous mCGH studies, our data indicated that genetic structuring as revealed by mCGH is stable over time and highly similar for isolates from different geographic origins. Conclusions Recombination comprising lateral transfer of entire genes as well as homologous intragenic recombination has a profound impact on meningococcal population structure and genome composition. Our data support the hypothesis that meningococcal virulence is polygenic in nature and that differences in metabolism might contribute to virulence. KW - population genetics KW - DNA recombination KW - meningococcal disease KW - recombinant proteins KW - genomic databases KW - comparative genomics KW - neisseria meningitidis KW - homologous recombination Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137960 VL - 6 IS - 4 ER -