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


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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Figure 1: Liposomes composed of cholesterol and sphingomyelin protect monocytes from cholesterol-dependent cytolysins, α-hemolysin (HML) and phospholipase C (PLC).
Figure 2: Cholesterol:sphingomyelin (Ch:Sm) liposomes protect epithelial and endothelial cells from lysis by pneumolysin (PLY) or phospholipase C (PLC).
Figure 3: Liposomes protect monocytes from toxins secreted by S. pyogenes, S. pneumoniae and S. aureus.
Figure 4: A mixture of cholesterol:sphingomyelin (Ch:Sm) + Sm-only liposomes confers survival in mice infected with S. pneumoniae.
Figure 5: A mixture of cholesterol:sphingomyelin (Ch:Sm) + Sm-only liposomes confer survival in mice infected with S. aureus.
Figure 6: A combination of toxin-sequestration with antibiotic treatment to treat fatal S. aureus and S. pneumoniae infections.


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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.

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B.D.H., D.R.N. and K.A.B. contributed equally to this study. B.D.H., K.A.B., R.Z., M.J.E. and E.G. performed in vivo experiments with S. aureus. D.R.N., S.G. and L.B.-M. performed in vivo experiments with S. pneumoniae. K.M. and J.S. provided bacterial culture supernatants for the in vitro experiments; J.S. performed MBC experiments; B.K. and L.J. performed bio-distribution experiments. M.L., H.W., A.D. and E.B.B. performed in vitro experiments; E.G. and A.K. designed the in vivo experiments with S. aureus and S. pneumoniae, respectively, and provided bacterial culture supernatants for the in vitro experiments. A.K. provided purified pneumolysin for in vitro experiments. E.B.B. designed the in vitro experiments. A.S. provided statistical advice for the paper. A.D. designed the study. E.B.B. designed and coordinated the study and wrote the paper. D.R.N., E.G., A.S., A.K. and A.D. edited and contributed to the writing of the paper. All authors analyzed and discussed the results and commented on the manuscript. E.G., A.K., A.D. and E.B.B. are co-senior authors.

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Correspondence to Eduard B Babiychuk.

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E.B.B. and A.D. are inventors on a patent application pertaining to this work.

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Henry, B., Neill, D., Becker, K. et al. Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice. Nat Biotechnol 33, 81–88 (2015).

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