New antiseptic peptides to protect against endotoxin-mediated shock
Systemic bacterial infections are associated with high mortality. The access of bacteria or constituents thereof to systemic circulation induces the massive release of immunomodulatory mediators, ultimately causing tissue hypoperfusion and multiple-organ failure despite adequate antibiotic treatment...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | info:eu-repo/semantics/article |
| Language: | eng |
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American Society for Microbiology
2013
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| Online Access: | https://hdl.handle.net/10171/29492 |
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| author | Gutsmann, T. (Thomas) Razquin-Olazaran, I. (Iosu) Kowalski, I. (Ina) Kaconis, Y. (Yani) Howe, J. (Jörg) Bartels, R. (Rainer) Hornef, M. (Mathias) Schürholz, T. (Tobias) Rossle, M. (Manfred) Sánchez-Gómez, S. (Susana) Moriyon, I. (Ignacio) Martinez-de-Tejada, G. (Guillermo) Brandenburg, K. (Klaus) |
| author_facet | Gutsmann, T. (Thomas) Razquin-Olazaran, I. (Iosu) Kowalski, I. (Ina) Kaconis, Y. (Yani) Howe, J. (Jörg) Bartels, R. (Rainer) Hornef, M. (Mathias) Schürholz, T. (Tobias) Rossle, M. (Manfred) Sánchez-Gómez, S. (Susana) Moriyon, I. (Ignacio) Martinez-de-Tejada, G. (Guillermo) Brandenburg, K. (Klaus) |
| author_sort | Gutsmann, T. (Thomas) |
| collection | DSpace |
| description | Systemic bacterial infections are associated with high mortality. The access of bacteria or constituents thereof to systemic circulation induces the massive release of immunomodulatory mediators, ultimately causing tissue hypoperfusion and multiple-organ failure despite adequate antibiotic treatment. Lipid A, the "endotoxic principle" of bacterial lipopolysaccharide (LPS), is one of the major bacterial immunostimuli. Here we demonstrate the biological efficacy of rationally designed new synthetic antilipopolysaccharide peptides (SALPs) based on the Limulus anti-LPS factor for systemic application. We show efficient inhibition of LPS-induced cytokine release and protection from lethal septic shock in vivo, whereas cytotoxicity was not observed under physiologically relevant conditions and concentrations. The molecular mechanism of LPS neutralization was elucidated by biophysical techniques. The lipid A part of LPS is converted from its "endotoxic conformation," the cubic aggregate structure, into an inactive multilamellar structure, and the binding affinity of the peptide to LPS exceeds those of known LPS-binding proteins, such as LPS-binding protein (LBP). Our results thus delineate a novel therapeutic strategy for the clinical management of patients with septic shock. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-29492 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2013 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-294922020-12-02T17:12:34Z New antiseptic peptides to protect against endotoxin-mediated shock Gutsmann, T. (Thomas) Razquin-Olazaran, I. (Iosu) Kowalski, I. (Ina) Kaconis, Y. (Yani) Howe, J. (Jörg) Bartels, R. (Rainer) Hornef, M. (Mathias) Schürholz, T. (Tobias) Rossle, M. (Manfred) Sánchez-Gómez, S. (Susana) Moriyon, I. (Ignacio) Martinez-de-Tejada, G. (Guillermo) Brandenburg, K. (Klaus) Antimicrobial peptide Escherichia coli In vitro Lipid A Lipopolysaccharide Neutralization Sepsis Detoxification Antibacterial Binding Systemic bacterial infections are associated with high mortality. The access of bacteria or constituents thereof to systemic circulation induces the massive release of immunomodulatory mediators, ultimately causing tissue hypoperfusion and multiple-organ failure despite adequate antibiotic treatment. Lipid A, the "endotoxic principle" of bacterial lipopolysaccharide (LPS), is one of the major bacterial immunostimuli. Here we demonstrate the biological efficacy of rationally designed new synthetic antilipopolysaccharide peptides (SALPs) based on the Limulus anti-LPS factor for systemic application. We show efficient inhibition of LPS-induced cytokine release and protection from lethal septic shock in vivo, whereas cytotoxicity was not observed under physiologically relevant conditions and concentrations. The molecular mechanism of LPS neutralization was elucidated by biophysical techniques. The lipid A part of LPS is converted from its "endotoxic conformation," the cubic aggregate structure, into an inactive multilamellar structure, and the binding affinity of the peptide to LPS exceeds those of known LPS-binding proteins, such as LPS-binding protein (LBP). Our results thus delineate a novel therapeutic strategy for the clinical management of patients with septic shock. 2013-07-04T12:36:21Z 2013-07-04T12:36:21Z 2010 info:eu-repo/semantics/article https://hdl.handle.net/10171/29492 eng info:eu-repo/semantics/openAccess application/pdf American Society for Microbiology |
| spellingShingle | Antimicrobial peptide Escherichia coli In vitro Lipid A Lipopolysaccharide Neutralization Sepsis Detoxification Antibacterial Binding Gutsmann, T. (Thomas) Razquin-Olazaran, I. (Iosu) Kowalski, I. (Ina) Kaconis, Y. (Yani) Howe, J. (Jörg) Bartels, R. (Rainer) Hornef, M. (Mathias) Schürholz, T. (Tobias) Rossle, M. (Manfred) Sánchez-Gómez, S. (Susana) Moriyon, I. (Ignacio) Martinez-de-Tejada, G. (Guillermo) Brandenburg, K. (Klaus) New antiseptic peptides to protect against endotoxin-mediated shock |
| title | New antiseptic peptides to protect against endotoxin-mediated shock |
| title_full | New antiseptic peptides to protect against endotoxin-mediated shock |
| title_fullStr | New antiseptic peptides to protect against endotoxin-mediated shock |
| title_full_unstemmed | New antiseptic peptides to protect against endotoxin-mediated shock |
| title_short | New antiseptic peptides to protect against endotoxin-mediated shock |
| title_sort | new antiseptic peptides to protect against endotoxin-mediated shock |
| topic | Antimicrobial peptide Escherichia coli In vitro Lipid A Lipopolysaccharide Neutralization Sepsis Detoxification Antibacterial Binding |
| url | https://hdl.handle.net/10171/29492 |
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