title: Lack of Sphingosine Causes Susceptibility to Pulmonary Staphylococcus Aureus Infections in Cystic Fibrosis.
abstract: BACKGROUND
  Pulmonary Staphylococcus aureus (S. aureus) infections occur early in a high percentage of cystic fibrosis (CF) patients and it is believed that these infections facilitate further colonization of CF lungs with Pseudomonas aeruginosa (P. aeruginosa). Previous studies demonstrated a marked reduction of sphingosine in tracheal and bronchial epithelial cells in CF compared to wild type mice, while ceramide is massively increased in CF mice.
  
  
  METHODS
  We investigated the effect of C18-sphingosine and C16-ceramide on S. aureus in vitro. Based on our results we performed pulmonary infections with S. aureus and tested the influence of sphingosine inhalation.
  
  
  RESULTS
  In vitro incubation of S. aureus with C18-sphingosine rapidly killed S. aureus, while C16-ceramide did not affect bacterial survival, but abrogated the effect of C18-sphingosine when applied together. The in vivo infection experiments revealed a high susceptibility of CF mice to pulmonary infection with S. aureus. Inhalation of C18-sphingosine rescued CF mice from pulmonary infections with different clinical S. aureus isolates, including a methicillin-resistant S. aureus (MRSA) strain.
  
  
  CONCLUSIONS
  Our data indicate that the imbalance between ceramide and sphingosine in the CF respiratory tract prevents killing of S. aureus and causes the high susceptibility of CF mice to pulmonary S. aureus infections.
authors.forename: Shaghayegh
authors.initials: S
authors.lastname: Tavakoli Tabazavareh
authors.forename: Aaron
authors.initials: A
authors.lastname: Seitz
authors.forename: Peter
authors.initials: P
authors.lastname: Jernigan
authors.forename: Carolin
authors.initials: C
authors.lastname: Sehl
authors.forename: Simone
authors.initials: S
authors.lastname: Keitsch
authors.forename: Stephan
authors.initials: S
authors.lastname: Lang
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Kahl
authors.forename: Michael
authors.initials: M
authors.lastname: Edwards
authors.forename: Heike
authors.initials: H
authors.lastname: Grassmé
authors.forename: Erich
authors.initials: E
authors.lastname: Gulbins
authors.forename: Katrin Anne
authors.initials: KA
authors.lastname: Becker
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D002518:Ceramides / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D003550:Cystic Fibrosis / Q000150:complications* / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000382:microbiology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D011023:Pneumonia, Staphylococcal / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D013110:Sphingosine / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D002518:Ceramides; D013110:Sphingosine