@article{BlaettnerDasPaprotkaetal.2016,
  author    = {Bl{\"a}ttner, Sebastian and Das, Sudip and Paprotka, Kerstin and Eilers, Ursula and Krischke, Markus and Kretschmer, Dorothee and Remmele, Christian W. and Dittrich, Marcus and M{\"u}ller, Tobias and Schuelein-Voelk, Christina and Hertlein, Tobias and Mueller, Martin J. and Huettel, Bruno and Reinhardt, Richard and Ohlsen, Knut and Rudel, Thomas and Fraunholz, Martin J.},
  title     = {Staphylococcus aureus Exploits a Non-ribosomal Cyclic Dipeptide to Modulate Survival within Epithelial Cells and Phagocytes},
  series = {PLoS Pathogens},
  volume    = {12},
  journal   = {PLoS Pathogens},
  number    = {9},
  doi       = {10.1371/journal.ppat.1005857},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180380},
  year      = {2016},
  abstract  = {Community-acquired (CA) Staphylococcus aureus cause various diseases even in healthy individuals. Enhanced virulence of CA-strains is partly attributed to increased production of toxins such as phenol-soluble modulins (PSM). The pathogen is internalized efficiently by mammalian host cells and intracellular S. aureus has recently been shown to contribute to disease. Upon internalization, cytotoxic S. aureus strains can disrupt phagosomal membranes and kill host cells in a PSM-dependent manner. However, PSM are not sufficient for these processes. Here we screened for factors required for intracellular S. aureus virulence. We infected escape reporter host cells with strains from an established transposon mutant library and detected phagosomal escape rates using automated microscopy. We thereby, among other factors, identified a non-ribosomal peptide synthetase (NRPS) to be required for efficient phagosomal escape and intracellular survival of S. aureus as well as induction of host cell death. By genetic complementation as well as supplementation with the synthetic NRPS product, the cyclic dipeptide phevalin, wild-type phenotypes were restored. We further demonstrate that the NRPS is contributing to virulence in a mouse pneumonia model. Together, our data illustrate a hitherto unrecognized function of the S. aureus NRPS and its dipeptide product during S. aureus infection.},
  language  = {en}
}
@article{HanzelmannJooFranzWachteletal.2016,
  author    = {Hanzelmann, Dennis and Joo, Hwang-Soo and Franz-Wachtel, Mirita and Hertlein, Tobias and Stevanovic, Stefan and Macek, Boris and Wolz, Christiane and G{\"o}tz, Friedrich and Otto, Michael and Kretschmer, Dorothee and Peschel, Andreas},
  title     = {Toll-like receptor 2 activation depends on lipopeptide shedding by bacterial surfactants},
  series = {Nature Communications},
  volume    = {7},
  journal   = {Nature Communications},
  doi       = {10.1038/ncomms12304},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165975},
  pages     = {12304},
  year      = {2016},
  abstract  = {Sepsis caused by Gram-positive bacterial pathogens is a major fatal disease but its molecular basis remains elusive. Toll-like receptor 2 (TLR2) has been implicated in the orchestration of inflammation and sepsis but its role appears to vary for different pathogen species and clones. Accordingly, Staphylococcus aureus clinical isolates differ substantially in their capacity to activate TLR2. Here we show that strong TLR2 stimulation depends on high-level production of phenol-soluble modulin (PSM) peptides in response to the global virulence activator Agr. PSMs are required for mobilizing lipoproteins, the TLR2 agonists, from the staphylococcal cytoplasmic membrane. Notably, the course of sepsis caused by PSM-deficient S. aureus is similar in wild-type and TLR2-deficient mice, but TLR2 is required for protection of mice against PSM-producing S. aureus. Thus, a crucial role of TLR2 depends on agonist release by bacterial surfactants. Modulation of this process may lead to new therapeutic strategies against Gram-positive infections.},
  language  = {en}
}