TY  - JOUR
A1  - Pewzner-Jung, Yael
A1  - Tabazavareh, Shaghayegh Tavakoli
A1  - Grassme, Heike
A1  - Becker, Katrin Anne
A1  - Japtok, Lukasz
A1  - Steinmann, Joerg
A1  - Joseph, Tammar
A1  - Lang, Stephan
A1  - Tuemmler, Burkhard
A1  - Schuchman, Edward H.
A1  - Lentsch, Alex B.
A1  - Kleuser, Burkhard
A1  - Edwards, Michael J.
A1  - Futerman, Anthony H.
A1  - Gulbins, Erich
T1  - Sphingoid long chain bases prevent lung infection by Pseudomonas aeruginosa
JF  - EMBO molecular medicine
N2  - 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.
KW  - cystic fibrosis
KW  - long chain base
KW  - lung infection
KW  - Pseudomonas aeruginosa
KW  - sphingosine
Y1  - 2014
U6  - https://doi.org/10.15252/emmm.201404075
SN  - 1757-4676
SN  - 1757-4684
VL  - 6
IS  - 9
SP  - 1205
EP  - 1214
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Henry, Brian D.
A1  - Neill, Daniel R.
A1  - Becker, Katrin Anne
A1  - Gore, Suzanna
A1  - Bricio-Moreno, Laura
A1  - Ziobro, Regan
A1  - Edwards, Michael J.
A1  - Muehlemann, Kathrin
A1  - Steinmann, Joerg
A1  - Kleuser, Burkhard
A1  - Japtok, Lukasz
A1  - Luginbuehl, Miriam
A1  - Wolfmeier, Heidi
A1  - Scherag, Andre
A1  - Gulbins, Erich
A1  - Kadioglu, Aras
A1  - Draeger, Annette
A1  - Babiychuk, Eduard B.
T1  - Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice
JF  - Nature biotechnology : the science and business of biotechnology
N2  - Gram-positive bacterial pathogens that secrete cytotoxic pore-forming toxins, such as Staphylococcus aureus and Streptococcus pneumoniae, cause a substantial burden of disease. Inspired by the principles that govern natural toxin-host interactions, we have engineered artificial liposomes that are tailored to effectively compete with host cells for toxin binding. Liposome-bound toxins are unable to lyse mammalian cells in vitro. We use these artificial liposomes as decoy targets to sequester bacterial toxins that are produced during active infection in vivo. Administration of artificial liposomes within 10 h after infection rescues mice from septicemia caused by S. aureus and S. pneumoniae, whereas untreated mice die within 24-33 h. Furthermore, liposomes protect mice against invasive pneumococcal pneumonia. Composed exclusively of naturally occurring lipids, tailored liposomes are not bactericidal and could be used therapeutically either alone or in conjunction with antibiotics to combat bacterial infections and to minimize toxin-induced tissue damage that occurs during bacterial clearance.
Y1  - 2015
U6  - https://doi.org/10.1038/nbt.3037
SN  - 1087-0156
SN  - 1546-1696
VL  - 33
IS  - 1
SP  - 81
EP  - U295
PB  - Nature Publ. Group
CY  - New York
ER  -