Brian D. Henry, Daniel R. Neill, Katrin Anne Becker, Suzanna Gore, Laura Bricio-Moreno, Regan Ziobro, Michael J. Edwards, Kathrin Muehlemann, Joerg Steinmann, Burkhard Kleuser, Lukasz Japtok, Miriam Luginbuehl, Heidi Wolfmeier, Andre Scherag, Erich Gulbins, Aras Kadioglu, Annette Draeger, Eduard B. Babiychuk
- 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 minimizeGram-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.…
MetadatenVerfasserangaben: | Brian D. Henry, Daniel R. Neill, Katrin Anne BeckerORCiDGND, Suzanna Gore, Laura Bricio-Moreno, Regan Ziobro, Michael J. Edwards, Kathrin Muehlemann, Joerg Steinmann, Burkhard KleuserORCiDGND, Lukasz JaptokGND, Miriam Luginbuehl, Heidi Wolfmeier, Andre Scherag, Erich GulbinsORCiDGND, Aras Kadioglu, Annette Draeger, Eduard B. Babiychuk |
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DOI: | https://doi.org/10.1038/nbt.3037 |
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ISSN: | 1087-0156 |
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ISSN: | 1546-1696 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/25362245 |
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Titel des übergeordneten Werks (Englisch): | Nature biotechnology : the science and business of biotechnology |
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Verlag: | Nature Publ. Group |
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Verlagsort: | New York |
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Publikationstyp: | Wissenschaftlicher Artikel |
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Sprache: | Englisch |
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Jahr der Erstveröffentlichung: | 2015 |
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Erscheinungsjahr: | 2015 |
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Datum der Freischaltung: | 27.03.2017 |
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Band: | 33 |
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Ausgabe: | 1 |
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Seitenanzahl: | 11 |
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Erste Seite: | 81 |
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Letzte Seite: | U295 |
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Fördernde Institution: | University of Bern, Commission for Technology and Innovation (CTI)
[16001.1 PFLS-LS]; Deutsche Forschungsgemeinschaft (DFG) [GU 335/16-2,
SFB 1112]; Federal Ministry of Education and Research (BMBF) (FKZ)
[01EO1002]; Institute of Infection & Global Health, University of
Liverpool |
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Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
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Peer Review: | Referiert |
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