@article{GulbinsSchumacherBeckeretal.2018,
  author    = {Gulbins, Anne and Schumacher, Fabian and Becker, Katrin Anne and Wilker, Barbara and Soddemann, Matthias and Boldrin, Francesco and M{\"u}ller, Christian P. and Edwards, Michael J. and Goodman, Michael and Caldwell, Charles C. and Kleuser, Burkhard and Kornhuber, Johannes and Szabo, Ildiko and Gulbins, Erich},
  title     = {Antidepressants act by inducing autophagy controlled by sphingomyelin-ceramide},
  series = {Molecular psychiatry},
  volume    = {23},
  journal   = {Molecular psychiatry},
  number    = {12},
  publisher = {Nature Publ. Group},
  address   = {London},
  issn      = {1359-4184},
  doi       = {10.1038/s41380-018-0090-9},
  pages     = {2324 -- 2346},
  year      = {2018},
  abstract  = {Major depressive disorder (MDD) is a common and severe disease characterized by mood changes, somatic alterations, and often suicide. MDD is treated with antidepressants, but the molecular mechanism of their action is unknown. We found that widely used antidepressants such as amitriptyline and fluoxetine induce autophagy in hippocampal neurons via the slow accumulation of sphingomyelin in lysosomes and Golgi membranes and of ceramide in the endoplasmic reticulum (ER). ER ceramide stimulates phosphatase 2A and thereby the autophagy proteins Ulk, Beclin, Vps34/Phosphatidylinositol 3-kinase, p62, and Lc3B. Although treatment with amitriptyline or fluoxetine requires at least 12 days to achieve sphingomyelin accumulation and the subsequent biochemical and cellular changes, direct inhibition of sphingomyelin synthases with tricyclodecan-9-yl-xanthogenate (D609) results in rapid (within 3 days) accumulation of ceramide in the ER, activation of autophagy, and reversal of biochemical and behavioral signs of stress-induced MDD. Inhibition of Beclin blocks the antidepressive effects of amitriptyline and D609 and induces cellular and behavioral changes typical of MDD. These findings identify sphingolipid-controlled autophagy as an important target for antidepressive treatment methods and provide a rationale for the development of novel antidepressants that act within a few days.},
  language  = {en}
}
@article{SeitzSchumacherBakeretal.2019,
  author    = {Seitz, Aaron P. and Schumacher, Fabian and Baker, Jennifer and Soddemann, Matthias and Wilker, Barbara and Caldwell, Charles C. and Gobble, Ryan M. and Kamler, Markus and Becker, Katrin Anne and Beck, Sascha and Kleuser, Burkhard and Edwards, Michael J. and Gulbins, Erich},
  title     = {Sphingosine-coating of plastic surfaces prevents ventilator-associated pneumonia},
  series = {Journal of molecular medicine},
  volume    = {97},
  journal   = {Journal of molecular medicine},
  number    = {8},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {0946-2716},
  doi       = {10.1007/s00109-019-01800-1},
  pages     = {1195 -- 1211},
  year      = {2019},
  abstract  = {Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in critically ill patients. Here, we employed the broad antibacterial effects of sphingosine to prevent VAP by developing a novel method of coating surfaces of endotracheal tubes with sphingosine and sphingosine analogs. Sphingosine and phytosphingosine coatings of endotracheal tubes prevent adherence and mediate killing of Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus, even in biofilms. Most importantly, sphingosine-coating of endotracheal tubes also prevented P. aeruginosa and S. aureus pneumonia in vivo. Coating of the tubes with sphingosine was stable, without obvious side effects on tracheal epithelial cells and did not induce inflammation. In summary, we describe a novel method to coat plastic surfaces and provide evidence for the application of sphingosine and phytosphingosine as novel antimicrobial coatings to prevent bacterial adherence and induce killing of pathogens on the surface of endotracheal tubes with potential to prevent biofilm formation and VAP.Key messagesNovel dip-coating method to coat plastic surfaces with lipids.Sphingosine and phytosphingosine as novel antimicrobial coatings on plastic surface.Sphingosine coatings of endotracheal tubes prevent bacterial adherence and biofilms.Sphingosine coatings of endotracheal tubes induce killing of pathogens.Sphingosine coatings of endotracheal tubes ventilator-associated pneumonia.},
  language  = {en}
}