title: Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice.
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.
authors.affiliation: 1] Institute of Molecular Biology, University of Duisburg-Essen, Essen, Germany. [2] Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Henry
authors.affiliation: Department of Clinical Infection Microbiology &Immunology, Institute of Infection &Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Neill
authors.affiliation: Institute of Molecular Biology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Katrin Anne
authors.initials: KA
authors.lastname: Becker
authors.affiliation: Department of Clinical Infection Microbiology &Immunology, Institute of Infection &Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Suzanna
authors.initials: S
authors.lastname: Gore
authors.affiliation: Department of Clinical Infection Microbiology &Immunology, Institute of Infection &Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Bricio-Moreno
authors.affiliation: 1] Institute of Molecular Biology, University of Duisburg-Essen, Essen, Germany. [2] Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Regan
authors.initials: R
authors.lastname: Ziobro
authors.affiliation: Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Edwards
authors.affiliation: Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Mühlemann
authors.affiliation: Institute of Medical Microbiology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinmann
authors.affiliation: Department of Toxicology, Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kleuser
authors.affiliation: Department of Toxicology, Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Japtok
authors.affiliation: Institute of Anatomy, University of Bern, Bern, Switzerland.
authors.forename: Miriam
authors.initials: M
authors.lastname: Luginbühl
authors.affiliation: Institute of Anatomy, University of Bern, Bern, Switzerland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Wolfmeier
authors.affiliation: Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Scherag
authors.affiliation: 1] Institute of Molecular Biology, University of Duisburg-Essen, Essen, Germany. [2] Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Erich
authors.initials: E
authors.lastname: Gulbins
authors.affiliation: Department of Clinical Infection Microbiology &Immunology, Institute of Infection &Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Aras
authors.initials: A
authors.lastname: Kadioglu
authors.affiliation: Institute of Anatomy, University of Bern, Bern, Switzerland.
authors.forename: Annette
authors.initials: A
authors.lastname: Draeger
authors.affiliation: Institute of Anatomy, University of Bern, Bern, Switzerland.
authors.forename: Eduard B
authors.initials: EB
authors.lastname: Babiychuk
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000517:prevention & control*; D001427:Bacterial Toxins / Q000737:chemistry*; D005098:Exotoxins / Q000737:chemistry*; D005818:Genetic Engineering; D008081:Liposomes / Q000737:chemistry*; D051379:Mice
chemical_list: D001427:Bacterial Toxins; D005098:Exotoxins; D008081:Liposomes