Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice

Brian D. Henry, Daniel R. Neill, Katrin Anne Becker, Suzanna Gore, Laura Bricio-Moreno, Regan Ziobro, Michael J. Edwards, Kathrin Mühlemann, Jörg Steinmann, Burkhard Kleuser, Lukasz Japtok, Miriam Luginbühl, Heidi Wolfmeier, André Scherag, Erich Gulbins, Aras Kadioglu, Annette Draeger, Eduard B. Babiychuk

Research output: Contribution to journalArticlepeer-review

175 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)81-88
Number of pages8
JournalNature Biotechnology
Volume33
Early online date2 Nov 2014
DOIs
Publication statusPublished - Jan 2015

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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