Coating of endotracheal tubes with sphingosine to prevent bacterial growth and ventilator-associated pneumonia
Final Report Abstract
The grant proposal aimed to investigate whether medical devices can be covalently or noncovalently coated with sphingosine or sphingosine derivatives (aim 1), whether these coatings are bactericidal in vitro and in vivo bactericidal (aim 2), whether the coatings are or are not cytotoxic for mammalian cells (aim 3) and whether we are able to prevent bacterial infections using sphingosine-/sphingosine-derivative-coated medical devices (aim 4). Our studies show that plastic and metal surfaces can be coated with sphingosine, phytosphingosine or stearylamine. The coatings result in a strong bactericidal effect against Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus and Staphylococcus epidermidis in vitro. Bacteria died within very short time. Sphingosine- and stearylamine coatings even killed pathogens in biofilms. The studies further revealed that covalently-bound sphingosine or derivatives were less bactericidal than a simple dip-coating method. Studies with a variety of sphingosine derivatives showed that none of these derivatives was superior to sphingosine in killing pathogens. In the dip-coating method we exposed the surface to a highly-concentrated sphingosine solution in an organic solvent for 3 sec., let the samples dry and repeated this process 3-times. These studies demonstrated that plastic and different metal surfaces are very efficiently coated with sphingosine using this dip-coating method developed by us. In vivo experiments showed that sphingosine coating of ventilation tubes prevented induced and spontaneous ventilation-induced pneumonia.
Publications
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Antibacterial activity of ceramide and ceramide analogs against pathogenic Neisseria. Sci. Rep. 2017:7:17627
Becam J, Walter T, Burgert A, Schlegel J, Sauer M, Seibel J, Schubert-Unkmeir A
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Sphingosine-coating of plastic surfaces prevents ventilator-associated pneumonia. J Mol Med (Berl) 2019;97:1195- 1211
eitz AP, Schumacher F, Baker J, Soddemann M, Wilker B, Caldwell CC, Gobble RM, Kamler M, Becker KA, Beck S, Kleuser B, Edwards MJ, Gulbins E
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Sphingosine is able to prevent and eliminate Staphylococcus epidermidis biofilm formation on different orthopedic implant materials in vitro. J Mol Med (Berl) 2020;98:209-219
Beck S, Sehl C, Voortmann S, Verhasselt HL, Edwards MJ, Buer J, Hasenberg M, Gulbins E, Becker KA
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Sphingosine kills bacteria by binding to cardiolipin. J Biol Chem 2020;295:7686-7696
Verhaegh R, Becker KA, Edwards MJ, Gulbins E
