@article{MeynersWawrzinekKraemeretal.2014,
  author    = {Meyners, Christian and Wawrzinek, Robert and Kraemer, Andreas and Hinz, Steffen and Wessig, Pablo and Meyer-Almes, Franz-Josef},
  title     = {A fluorescence lifetime-based binding assay for acetylpolyamine amidohydrolases from Pseudomonas aeruginosa using a [1,3]dioxolo[4,5-f][1,3]benzodioxole (DBD) ligand probe},
  series = {Analytical \& bioanalytical chemistry},
  volume    = {406},
  journal   = {Analytical \& bioanalytical chemistry},
  number    = {20},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {1618-2642},
  doi       = {10.1007/s00216-014-7886-5},
  pages     = {4889 -- 4897},
  year      = {2014},
  abstract  = {High-throughput assays for drug screening applications have to fulfill particular specifications. Besides the capability to identify even compounds with low potency, one of the major issues is to minimize the number of false-positive hits in a screening campaign in order to reduce the logistic effort for the subsequent cherry picking and confirmation procedure. In this respect, fluorescence lifetime (FLT) appears as an ideal readout parameter that is supposed to be robust against autofluorescent and light-absorbing compounds, the most common source of systematic false positives. The extraordinary fluorescence features of the recently discovered [1,3]dioxolo[4,5-f][1,3]benzodioxole dyes were exploited to develop an FLT-based binding assay with exceptionally robust readout. The assay setup was comprehensively validated and shown to comply not only with all requirements for a powerful high-throughput screening assay but also to be suitable to determine accurate binding constants for inhibitors against enzymes of the histone deacetylase family. Using the described binding assay, the first inhibitors against three members of this enzyme family from Pseudomonas aeruginosa were identified. The compounds were characterized in terms of potency and selectivity profile. The novel ligand probe should also be applicable to other homologues of the histone deacetylase family that are inhibited by N-hydroxy-N'-phenyloctandiamide.},
  language  = {en}
}
@article{PewznerJungTabazavarehGrassmeetal.2014,
  author    = {Pewzner-Jung, Yael and Tabazavareh, Shaghayegh Tavakoli and Grassme, Heike and Becker, Katrin Anne and Japtok, Lukasz and Steinmann, Joerg and Joseph, Tammar and Lang, Stephan and Tuemmler, Burkhard and Schuchman, Edward H. and Lentsch, Alex B. and Kleuser, Burkhard and Edwards, Michael J. and Futerman, Anthony H. and Gulbins, Erich},
  title     = {Sphingoid long chain bases prevent lung infection by Pseudomonas aeruginosa},
  series = {EMBO molecular medicine},
  volume    = {6},
  journal   = {EMBO molecular medicine},
  number    = {9},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {1757-4676},
  doi       = {10.15252/emmm.201404075},
  pages     = {1205 -- 1214},
  year      = {2014},
  abstract  = {Cystic fibrosis patients and patients with chronic obstructive pulmonary disease, trauma, burn wound, or patients requiring ventilation are susceptible to severe pulmonary infection by Pseudomonas aeruginosa. Physiological innate defense mechanisms against this pathogen, and their alterations in lung diseases, are for the most part unknown. We now demonstrate a role for the sphingoid long chain base, sphingosine, in determining susceptibility to lung infection by P.aeruginosa. Tracheal and bronchial sphingosine levels were significantly reduced in tissues from cystic fibrosis patients and from cystic fibrosis mouse models due to reduced activity of acid ceramidase, which generates sphingosine from ceramide. Inhalation of mice with sphingosine, with a sphingosine analog, FTY720, or with acid ceramidase rescued susceptible mice from infection. Our data suggest that luminal sphingosine in tracheal and bronchial epithelial cells prevents pulmonary P.aeruginosa infection in normal individuals, paving the way for novel therapeutic paradigms based on inhalation of acid ceramidase or of sphingoid long chain bases in lung infection.},
  language  = {en}
}