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

doi:10.1038/nbt.3037

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

Molecular Microbiology

Research output: Contribution to journal › Article › peer-review

187 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 language	English
Pages (from-to)	81-88
Number of pages	8
Journal	Nature Biotechnology
Volume	33
Early online date	2 Nov 2014
DOIs	https://doi.org/10.1038/nbt.3037
Publication status	Published - Jan 2015

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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Henry, B. D., Neill, D. R., Becker, K. A., Gore, S., Bricio-Moreno, L., Ziobro, R., Edwards, M. J., Mühlemann, K., Steinmann, J., Kleuser, B., Japtok, L., Luginbühl, M., Wolfmeier, H., Scherag, A., Gulbins, E., Kadioglu, A., Draeger, A., & Babiychuk, E. B. (2015). Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice. Nature Biotechnology, 33, 81-88. https://doi.org/10.1038/nbt.3037

@article{b974de24a5fd4ae59f06132271921ef7,

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.",

author = "Henry, {Brian D.} and Neill, {Daniel R.} and Becker, {Katrin Anne} and Suzanna Gore and Laura Bricio-Moreno and Regan Ziobro and Edwards, {Michael J.} and Kathrin M{\"u}hlemann and J{\"o}rg Steinmann and Burkhard Kleuser and Lukasz Japtok and Miriam Luginb{\"u}hl and Heidi Wolfmeier and Andr{\'e} Scherag and Erich Gulbins and Aras Kadioglu and Annette Draeger and Babiychuk, {Eduard B.}",

note = "Funding Information: We gratefully acknowledge the financial support of the University of Bern, Commission for Technology and Innovation (CTI) (16001.1 PFLS-LS to A.D. and E.B.B.), Deutsche Forschungsgemeinschaft (DFG GU 335/16-2 to E.G. and SFB 1112 to B.K.), Federal Ministry of Education and Research (BMBF) (FKZ: 01EO1002 to A.S.) and the Institute of Infection & Global Health, University of Liverpool to A.K. Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",

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doi = "10.1038/nbt.3037",

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Henry, BD, Neill, DR, Becker, KA, Gore, S, Bricio-Moreno, L, Ziobro, R, Edwards, MJ, Mühlemann, K, Steinmann, J, Kleuser, B, Japtok, L, Luginbühl, M, Wolfmeier, H, Scherag, A, Gulbins, E, Kadioglu, A, Draeger, A & Babiychuk, EB 2015, 'Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice', Nature Biotechnology, vol. 33, pp. 81-88. https://doi.org/10.1038/nbt.3037

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AU - Henry, Brian D.

AU - Neill, Daniel R.

AU - Becker, Katrin Anne

AU - Gore, Suzanna

AU - Bricio-Moreno, Laura

AU - Ziobro, Regan

AU - Edwards, Michael J.

AU - Mühlemann, Kathrin

AU - Steinmann, Jörg

AU - Kleuser, Burkhard

AU - Japtok, Lukasz

AU - Luginbühl, Miriam

AU - Wolfmeier, Heidi

AU - Scherag, André

AU - Gulbins, Erich

AU - Kadioglu, Aras

AU - Draeger, Annette

AU - Babiychuk, Eduard B.

N1 - Funding Information: We gratefully acknowledge the financial support of the University of Bern, Commission for Technology and Innovation (CTI) (16001.1 PFLS-LS to A.D. and E.B.B.), Deutsche Forschungsgemeinschaft (DFG GU 335/16-2 to E.G. and SFB 1112 to B.K.), Federal Ministry of Education and Research (BMBF) (FKZ: 01EO1002 to A.S.) and the Institute of Infection & Global Health, University of Liverpool to A.K. Publisher Copyright: © 2015 Nature America, Inc.

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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.

AB - 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.

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DO - 10.1038/nbt.3037

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SN - 1087-0156

VL - 33

SP - 81

EP - 88

JO - Nature Biotechnology

JF - Nature Biotechnology

ER -

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

Abstract

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