{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:16:26Z","timestamp":1790946986542,"version":"4.1.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2014,11,2]],"date-time":"2014-11-02T00:00:00Z","timestamp":1414886400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Biotechnol"],"published-print":{"date-parts":[[2015,1]]},"DOI":"10.1038\/nbt.3037","type":"journal-article","created":{"date-parts":[[2014,11,2]],"date-time":"2014-11-02T15:15:08Z","timestamp":1414941308000},"page":"81-88","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":219,"title":["Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice"],"prefix":"10.1038","volume":"33","author":[{"given":"Brian D","family":"Henry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R","family":"Neill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin Anne","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanna","family":"Gore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bricio-Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regan","family":"Ziobro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"M\u00fchlemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Steinmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Kleuser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukasz","family":"Japtok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Luginb\u00fchl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Wolfmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Scherag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Gulbins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aras","family":"Kadioglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Draeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard B","family":"Babiychuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,11,2]]},"reference":[{"key":"BFnbt3037_CR1","doi-asserted-by":"publisher","first-page":"S19","DOI":"10.1016\/j.ijid.2010.05.009","volume":"14","author":"S Stefani","year":"2010","unstructured":"Stefani, S. & Goglio, A. Methicillin-resistant Staphylococcus aureus: related infections and antibiotic resistance. Int. J. Infect. Dis. 14. (suppl. 4), S19\u2013S22 (2010).","journal-title":"Int. J. Infect. Dis."},{"key":"BFnbt3037_CR2","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1038\/nrmicro2693","volume":"9","author":"K Bush","year":"2011","unstructured":"Bush, K. et al. Tackling antibiotic resistance. Nat. Rev. Microbiol. 9, 894\u2013896 (2011).","journal-title":"Nat. Rev. Microbiol."},{"key":"BFnbt3037_CR3","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/S0958-1669(00)00155-5","volume":"11","author":"LE Alksne","year":"2000","unstructured":"Alksne, L.E. & Projan, S.J. Bacterial virulence as a target for antimicrobial chemotherapy. Curr. Opin. Biotechnol. 11, 625\u2013636 (2000).","journal-title":"Curr. Opin. Biotechnol."},{"key":"BFnbt3037_CR4","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1128\/MMBR.57.2.347-366.1993","volume":"57","author":"RW Titball","year":"1993","unstructured":"Titball, R.W. Bacterial phospholipases C. Microbiol. Rev. 57, 347\u2013366 (1993).","journal-title":"Microbiol. Rev."},{"key":"BFnbt3037_CR5","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/nrmicro1871","volume":"6","author":"A Kadioglu","year":"2008","unstructured":"Kadioglu, A., Weiser, J.N., Paton, J.C. & Andrew, P.W. The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease. Nat. Rev. Microbiol. 6, 288\u2013301 (2008).","journal-title":"Nat. Rev. Microbiol."},{"key":"BFnbt3037_CR6","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1038\/nm1207-1405","volume":"13","author":"J Bubeck Wardenburg","year":"2007","unstructured":"Bubeck Wardenburg, J., Bae, T., Otto, M., DeLeo, F.R. & Schneewind, O. Poring over pores: \u03b1-hemolysin and Panton-Valentine leukocidin in Staphylococcus aureus pneumonia. Nat. Med. 13, 1405\u20131406 (2007).","journal-title":"Nat. Med."},{"key":"BFnbt3037_CR7","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1074\/jbc.M804632200","volume":"284","author":"AM Timmer","year":"2009","unstructured":"Timmer, A.M. et al. Streptolysin O promotes group A Streptococcus immune evasion by accelerated macrophage apoptosis. J. Biol. Chem. 284, 862\u2013871 (2009).","journal-title":"J. Biol. Chem."},{"key":"BFnbt3037_CR8","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1007\/s00018-007-7434-y","volume":"65","author":"MR Gonzalez","year":"2008","unstructured":"Gonzalez, M.R., Bischofberger, M., Pernot, L., van der Goot, F.G. & Freche, B. Bacterial pore-forming toxins: The (w)hole story? Cell. Mol. Life Sci. 65, 493\u2013507 (2008).","journal-title":"Cell. Mol. Life Sci."},{"key":"BFnbt3037_CR9","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.pbiomolbio.2004.01.009","volume":"88","author":"MW Parker","year":"2005","unstructured":"Parker, M.W. & Feil, S.C. Pore-forming protein toxins: from structure to function. Prog. Biophys. Mol. Biol. 88, 91\u2013142 (2005).","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"BFnbt3037_CR10","doi-asserted-by":"publisher","first-page":"6199","DOI":"10.1128\/IAI.73.10.6199-6209.2005","volume":"73","author":"RK Tweten","year":"2005","unstructured":"Tweten, R.K. Cholesterol-dependent cytolysins, a family of versatile pore-forming toxins. Infect. Immun. 73, 6199\u20136209 (2005).","journal-title":"Infect. Immun."},{"key":"BFnbt3037_CR11","doi-asserted-by":"publisher","first-page":"26014","DOI":"10.1074\/jbc.M601960200","volume":"281","author":"A Valeva","year":"2006","unstructured":"Valeva, A. et al. Evidence that clustered phosphocholine head groups serve as sites for binding and assembly of an oligomeric protein pore. J. Biol. cholesterolem. 281, 26014\u201326021 (2006).","journal-title":"J. Biol. cholesterolem."},{"key":"BFnbt3037_CR12","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1111\/j.1574-6976.2010.00231.x","volume":"34","author":"I Linhartov\u00e1","year":"2010","unstructured":"Linhartov\u00e1, I. et al. RTX proteins: a highly diverse family secreted by a common mechanism. FEMS Microbiol. Rev. 34, 1076\u20131112 (2010).","journal-title":"FEMS Microbiol. Rev."},{"key":"BFnbt3037_CR13","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1006\/anae.2001.0376","volume":"7","author":"I Olsen","year":"2001","unstructured":"Olsen, I. & Jantzen, E. Sphingolipids in bacteria and fungi. Anaerobe 7, 103\u2013112 (2001).","journal-title":"Anaerobe"},{"key":"BFnbt3037_CR14","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1038\/42408","volume":"387","author":"K Simons","year":"1997","unstructured":"Simons, K. & Ikonen, E. Functional rafts in cell membranes. Nature 387, 569\u2013572 (1997).","journal-title":"Nature"},{"key":"BFnbt3037_CR15","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/0092-8674(92)90189-J","volume":"68","author":"DA Brown","year":"1992","unstructured":"Brown, D.A. & Rose, J.K. Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface. Cell 68, 533\u2013544 (1992).","journal-title":"Cell"},{"key":"BFnbt3037_CR16","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/S0955-0674(97)80030-0","volume":"9","author":"T Harder","year":"1997","unstructured":"Harder, T. & Simons, K. Caveolae, DIGs, and the dynamics of sphingolipid-cholesterol microdomains. Curr. Opin. Cell Biol. 9, 534\u2013542 (1997).","journal-title":"Curr. Opin. Cell Biol."},{"key":"BFnbt3037_CR17","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/nrm2977","volume":"11","author":"K Simons","year":"2010","unstructured":"Simons, K. & Gerl, M.J. Revitalizing membrane rafts: new tools and insights. Nat. Rev. Mol. Cell Biol. 11, 688\u2013699 (2010).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"BFnbt3037_CR18","doi-asserted-by":"publisher","first-page":"30224","DOI":"10.1074\/jbc.M110.123554","volume":"285","author":"C Klose","year":"2010","unstructured":"Klose, C. et al. Yeast lipids can phase-separate into micrometer-scale membrane domains. J. Biol. Chem. 285, 30224\u201330232 (2010).","journal-title":"J. Biol. Chem."},{"key":"BFnbt3037_CR19","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/S0005-2736(98)00260-0","volume":"1417","author":"J Huang","year":"1999","unstructured":"Huang, J., Buboltz, J.T. & Feigenson, G.W. Maximum solubility of cholesterol in phosphatidylcholine and phosphatidylethanolamine bilayers. Biochim. Biophys. Acta 1417, 89\u2013100 (1999).","journal-title":"Biochim. Biophys. Acta"},{"key":"BFnbt3037_CR20","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1194\/jlr.R400004-JLR200","volume":"45","author":"JM Dietschy","year":"2004","unstructured":"Dietschy, J.M. & Turley, S.D. Cholesterol metabolism in the central nervous system during early development and in the mature animal. J. Lipid Res. 45, 1375\u20131397 (2004).","journal-title":"J. Lipid Res."},{"key":"BFnbt3037_CR21","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/nrm2336","volume":"9","author":"E Ikonen","year":"2008","unstructured":"Ikonen, E. Cellular cholesterol trafficking and compartmentalization. Nat. Rev. Mol. Cell Biol. 9, 125\u2013138 (2008).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"BFnbt3037_CR22","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.bbalip.2009.03.002","volume":"1791","author":"B Mesmin","year":"2009","unstructured":"Mesmin, B. & Maxfield, F.R. Intracellular sterol dynamics. Biochim. Biophys. Acta 1791, 636\u2013645 (2009).","journal-title":"Biochim. Biophys. Acta"},{"key":"BFnbt3037_CR23","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1038\/nri2402","volume":"8","author":"D Rittirsch","year":"2008","unstructured":"Rittirsch, D., Flierl, M.A. & Ward, P.A. Harmful molecular mechanisms in sepsis. Nat. Rev. Immunol. 8, 776\u2013787 (2008).","journal-title":"Nat. Rev. Immunol."},{"key":"BFnbt3037_CR24","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1006\/nbdi.2002.0561","volume":"11","author":"AK Stringaris","year":"2002","unstructured":"Stringaris, A.K. et al. Neurotoxicity of pneumolysin, a major pneumococcal virulence factor, involves calcium influx and depends on activation of p38 mitogen-activated protein kinase. Neurobiol. Dis. 11, 355\u2013368 (2002).","journal-title":"Neurobiol. Dis."},{"key":"BFnbt3037_CR25","doi-asserted-by":"publisher","first-page":"2649","DOI":"10.1128\/AAC.47.8.2649-2654.2003","volume":"47","author":"A Spreer","year":"2003","unstructured":"Spreer, A. et al. Reduced release of pneumolysin by Streptococcus pneumoniae in vitro and in vivo after treatment with nonbacteriolytic antibiotics in comparison to ceftriaxone. Antimicrob. Agents Chemother. 47, 2649\u20132654 (2003).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BFnbt3037_CR26","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1093\/cid\/cir926","volume":"54","author":"EC Wall","year":"2012","unstructured":"Wall, E.C. et al. Persistence of pneumolysin in the cerebrospinal fluid of patients with pneumococcal meningitis is associated with mortality. Clin. Infect. Dis. 54, 701\u2013705 (2012).","journal-title":"Clin. Infect. Dis."},{"key":"BFnbt3037_CR27","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1128\/AAC.45.5.1487-1492.2001","volume":"45","author":"IA Bakker-Woudenberg","year":"2001","unstructured":"Bakker-Woudenberg, I.A., ten Kate, M.T., Guo, L., Working, P. & Mouton, J.W. Improved efficacy of ciprofloxacin administered in polyethylene glycol-coated liposomes for treatment of Klebsiella pneumoniae pneumonia in rats. Antimicrob. Agents Chemother. 45, 1487\u20131492 (2001).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BFnbt3037_CR28","doi-asserted-by":"publisher","first-page":"2671","DOI":"10.1128\/AAC.38.11.2671","volume":"38","author":"GF Brisseau","year":"1994","unstructured":"Brisseau, G.F. et al. Unilamellar liposomes modulate secretion of tumor necrosis factor by lipopolysaccharide-stimulated macrophages. Antimicrob. Agents cholesterolemother. 38, 2671\u20132675 (1994).","journal-title":"Antimicrob. Agents cholesterolemother."},{"key":"BFnbt3037_CR29","doi-asserted-by":"publisher","first-page":"4581","DOI":"10.1128\/AAC.00115-11","volume":"55","author":"CL Moore","year":"2011","unstructured":"Moore, C.L. et al. Prediction of failure in vancomycin-treated methicillin-resistant Staphylococcus aureus bloodstream infection: a clinically useful risk stratification tool. Antimicrob. Agents Chemother. 55, 4581\u20134588 (2011).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BFnbt3037_CR30","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.jinf.2011.08.004","volume":"63","author":"R Huttunen","year":"2011","unstructured":"Huttunen, R. & Aittoniemi, J. New concepts in the pathogenesis, diagnosis and treatment of bacteremia and sepsis. J. Infect. 63, 407\u2013419 (2011).","journal-title":"J. Infect."},{"key":"BFnbt3037_CR31","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.ijpharm.2009.11.033","volume":"387","author":"Z Drulis-Kawa","year":"2010","unstructured":"Drulis-Kawa, Z. & Dorotkiewicz-Jach, A. Liposomes as delivery systems for antibiotics. Int. J. Pharm. 387, 187\u2013198 (2010).","journal-title":"Int. J. Pharm."},{"key":"BFnbt3037_CR32","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1038\/nrmicro3232","volume":"12","author":"RC Allen","year":"2014","unstructured":"Allen, R.C., Popat, R., Diggle, S.P. & Brown, S.P. Targeting virulence: can we make evolution-proof drugs? Nat. Rev. Microbiol. 12, 300\u2013308 (2014).","journal-title":"Nat. Rev. Microbiol."},{"key":"BFnbt3037_CR33","doi-asserted-by":"publisher","first-page":"e1001191","DOI":"10.1371\/journal.ppat.1001191","volume":"6","author":"EA McNeela","year":"2010","unstructured":"McNeela, E.A. et al. Pneumolysin activates the NLRP3 inflammasome and promotes proinflammatory cytokines independently of TLR4. PLoS Pathog. 6, e1001191 (2010).","journal-title":"PLoS Pathog."},{"key":"BFnbt3037_CR34","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1038\/cdd.2009.30","volume":"16","author":"EB Babiychuk","year":"2009","unstructured":"Babiychuk, E.B., Monastyrskaya, K., Potez, S. & Draeger, A. Intracellular Ca(2+) operates a switch between repair and lysis of streptolysin O-perforated cells. Cell Death Differ. 16, 1126\u20131134 (2009).","journal-title":"Cell Death Differ."},{"key":"BFnbt3037_CR35","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/317106a0","volume":"317","author":"DB Morton","year":"1985","unstructured":"Morton, D.B. Pain and laboratory animals. Nature 317, 106 (1985).","journal-title":"Nature"},{"key":"BFnbt3037_CR36","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.ymeth.2005.01.009","volume":"36","author":"AH Merrill Jr.","year":"2005","unstructured":"Merrill, A.H. Jr., Sullards, M.C., Allegood, J.C., Kelly, S. & Wang, E. Sphingolipidomics: high-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry. Methods 36, 207\u2013224 (2005).","journal-title":"Methods"},{"key":"BFnbt3037_CR37","unstructured":"Clinical and Laboratory Standards Institute. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically \u2013 Twenty second information supplement: Approved standard M07\u2013A8. (CLSI, Wayne, PA, USA, 2009)."},{"key":"BFnbt3037_CR38","first-page":"35","volume":"1","author":"H Shah","year":"2011","unstructured":"Shah, H. How to calculate sample size in animal studies. Natl. J. Physiol. Pharm. Pharmacol. 1, 35\u201339 (2011).","journal-title":"Natl. J. Physiol. Pharm. Pharmacol."}],"container-title":["Nature Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nbt.3037","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nbt.3037.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nbt.3037.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T14:29:11Z","timestamp":1684420151000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nbt.3037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,2]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["BFnbt3037"],"URL":"https:\/\/doi.org\/10.1038\/nbt.3037","relation":{},"ISSN":["1087-0156","1546-1696"],"issn-type":[{"value":"1087-0156","type":"print"},{"value":"1546-1696","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,2]]},"assertion":[{"value":"28 August 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2014","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 November 2014","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"E.B.B. and A.D. are inventors on a patent application pertaining to this work.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}