@article{SassVanAckerFoerstneretal.2015,
  author    = {Sass, Andrea M. and Van Acker, Heleen and F{\"o}rstner, Konrad U. and Van Nieuwerburgh, Filip and Deforce, Dieter and Vogel, J{\"o}rg and Coenye, Tom},
  title     = {Genome-wide transcription start site profiling in biofilm-grown Burkholderia cenocepacia J2315},
  series = {BMC Genomics},
  volume    = {16},
  journal   = {BMC Genomics},
  number    = {775},
  doi       = {10.1186/s12864-015-1993-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139748},
  year      = {2015},
  abstract  = {Background: Burkholderia cenocepacia is a soil-dwelling Gram-negative Betaproteobacterium with an important role as opportunistic pathogen in humans. Infections with B. cenocepacia are very difficult to treat due to their high intrinsic resistance to most antibiotics. Biofilm formation further adds to their antibiotic resistance. B. cenocepacia harbours a large, multi-replicon genome with a high GC-content, the reference genome of strain J2315 includes 7374 annotated genes. This study aims to annotate transcription start sites and identify novel transcripts on a whole genome scale. Methods: RNA extracted from B. cenocepacia J2315 biofilms was analysed by differential RNA-sequencing and the resulting dataset compared to data derived from conventional, global RNA-sequencing. Transcription start sites were annotated and further analysed according to their position relative to annotated genes. Results: Four thousand ten transcription start sites were mapped over the whole B. cenocepacia genome and the primary transcription start site of 2089 genes expressed in B. cenocepacia biofilms were defined. For 64 genes a start codon alternative to the annotated one was proposed. Substantial antisense transcription for 105 genes and two novel protein coding sequences were identified. The distribution of internal transcription start sites can be used to identify genomic islands in B. cenocepacia. A potassium pump strongly induced only under biofilm conditions was found and 15 non-coding small RNAs highly expressed in biofilms were discovered. Conclusions: Mapping transcription start sites across the B. cenocepacia genome added relevant information to the J2315 annotation. Genes and novel regulatory RNAs putatively involved in B. cenocepacia biofilm formation were identified. These findings will help in understanding regulation of B. cenocepacia biofilm formation.},
  language  = {en}
}
@article{GomesWestermannSauerweinetal.2019,
  author    = {Gomes, Sara F. Martins and Westermann, Alexander J. and Sauerwein, Till and Hertlein, Tobias and F{\"o}rstner, Konrad U. and Ohlsen, Knut and Metzger, Marco and Shusta, Eric V. and Kim, Brandon J. and Appelt-Menzel, Antje and Schubert-Unkmeir, Alexandra},
  title     = {Induced pluripotent stem cell-derived brain endothelial cells as a cellular model to study Neisseria meningitidis infection},
  series = {Frontiers in Microbiology},
  volume    = {10},
  journal   = {Frontiers in Microbiology},
  number    = {1181},
  doi       = {10.3389/fmicb.2019.01181},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201562},
  year      = {2019},
  abstract  = {Meningococcal meningitis is a severe central nervous system infection that occurs when Neisseria meningitidis (Nm) penetrates brain endothelial cells (BECs) of the meningeal blood-cerebrospinal fluid barrier. As a human-specific pathogen, in vivo models are greatly limited and pose a significant challenge. In vitro cell models have been developed, however, most lack critical BEC phenotypes limiting their usefulness. Human BECs generated from induced pluripotent stem cells (iPSCs) retain BEC properties and offer the prospect of modeling the human-specific Nm interaction with BECs. Here, we exploit iPSC-BECs as a novel cellular model to study Nm host-pathogen interactions, and provide an overview of host responses to Nm infection. Using iPSC-BECs, we first confirmed that multiple Nm strains and mutants follow similar phenotypes to previously described models. The recruitment of the recently published pilus adhesin receptor CD147 underneath meningococcal microcolonies could be verified in iPSC-BECs. Nm was also observed to significantly increase the expression of pro-inflammatory and neutrophil-specific chemokines IL6, CXCL1, CXCL2, CXCL8, and CCL20, and the secretion of IFN-γ and RANTES. For the first time, we directly observe that Nm disrupts the three tight junction proteins ZO-1, Occludin, and Claudin-5, which become frayed and/or discontinuous in BECs upon Nm challenge. In accordance with tight junction loss, a sharp loss in trans-endothelial electrical resistance, and an increase in sodium fluorescein permeability and in bacterial transmigration, was observed. Finally, we established RNA-Seq of sorted, infected iPSC-BECs, providing expression data of Nm-responsive host genes. Altogether, this model provides novel insights into Nm pathogenesis, including an impact of Nm on barrier properties and tight junction complexes, and suggests that the paracellular route may contribute to Nm traversal of BECs.},
  language  = {en}
}