P07

Overview:

Ventilator-associated pneumonia (VAP) is a serious clinical problem and an important cause of morbidity and mortality in critically ill patients. Bacterial infections of the upper airway combined with the development of bacterial biofilm on those tubes has proven to be an important factor. Our group was the first to show that sphingosine, a sphingolipid present in most eukaryotic membranes, is present in high concentrations in the respiratory epithelium and plays an important role in the innate immunity of the upper respiratory tract by preventing bacterial invasion into the lower airways [1].

We will now investigate whether sphingosine analogs can be (covalently) linked to polyvinyl chloride (PVC) tubes to obtain bactericidal surfaces without changing the material properties. Ultimately, we aim to determine whether endotracheal tubes coated with sphingosine analogs prevent local and systemic bacterial infections in vivo in a mouse model.  

Project related publications:

Collenburg L, Walter T, Burgert A, Müller N, Seibel J, Japtok L, Kleuser B, Sauer M, Schneider-Schaulies S. (2016) A functionalized sphingolipid analogue for studying redistribution during activation in living T cells. J. Immunol. Pii: 1502447. doi: 10.4049/​jimmunol.1502447

Claes D, Memmel E, Holzapfel M, Seibel J, Maison W. (2014) High-affinity carbohydrate binding by trimeric benzoboroxoles measured on carbohydrate arrays. Chembiochem. 15:2450-7.

Letschert S, Göhler A, Franke C, Bertleff-Zieschang N, Memmel E, Doose S, Seibel J, Sauer M. (2014) Super-resolution imaging of plasma membrane glycans. Angew. Chem. Int. Ed. Engl. 53:10921-4.

Memmel E, Homann A, Oelschlaeger TA, Seibel J. (2013) Metabolic glycoengineering of Staphylococcus aureus reduces its adherence to human T24 bladder carcinoma cells. Chem. Commun. (Camb.) 49:7301-3.

Homann A, Qamar RU, Serim S, Dersch P, Seibel J. (2010) Bioorthogonal metabolic glycoengineering of human larynx carcinoma (HEp-2) cells targeting sialic acid. Beilstein J. Org. Chem. 6:24. doi: 10.3762/bjoc.6.24.

Henry BD*, Neill DR*, Becker KA*, Gore S, Bricio-Moreno L, Ziobro R, Edwards MJ, Mühlemann K, Steinmann J, Kleuser B, Japtok L, Luginbühl M, Wolfmeier H, Scherag A, Gulbins E*, Kadioglu A*, Draeger A*, Babiychuk EB*. (2015) Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice. Nat. Biotechnol. 33:81-88. *Shared first authorship or senior authorship.

Pewzner-Jung Y, Tavakoli Tabazavareh S, Grassmé H, Becker KA, Japtok L, Steinmann J, Joseph T, Lang S, Tuemmler B, Schuchman EH, Lentsch AB, Kleuser B, Edwards MJ, Futerman AH, Gulbins E. (2014) Sphingoid long chain bases prevent lung infection by Pseudomonas aeruginosa. EMBO Mol. Med. 6:1205-1.

Teichgräber V, Ulrich M, Endlich N, Riethmüller J, Wilker B, De Oliveira-Munding CC, van Heeckeren AM, Barr ML, von Kürthy G, Schmid KW, Weller M, Tümmler B, Lang F, Grassmé H, Döring G, Gulbins E. (2008) Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis. Nat. Med. 14:382-91.

Grassmé H, Jendrossek V, Riehle A, von Kürthy G, Berger J, Schwarz H, Weller M, Kolesnick R, Gulbins E. (2003) Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts. Nat. Med. 9:322-30.

Grassmé H, Kirschnek S, Riethmueller J, Riehle A, von Kürthy G, Lang F, Weller M, Gulbins E. (2000) CD95/CD95 ligand interactions on epithelial cells in host defense to Pseudomonas aeruginosa. Science 290:527-30