Cathelicidin and PMB neutralize endotoxins by multifactorial mechanisms including LPS interaction and targeting of host cell membranes
Antimicrobial peptides (AMPs) contribute to an effective protection against infections. The antibacterial function of AMPs depends on their interactions with microbial membranes and lipids, such as lipopolysaccharide (LPS; endotoxin). Hyperinflammation induced by endotoxin is a key factor in bacteri...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | info:eu-repo/semantics/article |
| Language: | eng |
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PNAS
2024
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| Online Access: | https://hdl.handle.net/10171/68498 |
| _version_ | 1793400141436157952 |
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| author | Schromm, A.B. (Andra B.) Paulowski, L. (Laura) Kaconis, Y. (Yani) Kopp, F. (Franziska) Koistinen, M. (Max) Donoghue, A. (Annemarie) Keese, S. (Susanne) Nehls, C. (Christian) Wernecke, J. (Julia) Garidel, P. (Patrick) Sevcsik, E. (Eva) Lohner, K. (Karl) Sánchez-Gómez, S. (Susana) Martinez-de-Tejada, G. (Guillermo) Brandenburg, K. (Klaus) Brameshuber, M. (Mario) Schütz, G.J. (Gerhard J.) Andrä, J. (Jörg) Gutsmann, T. (Thomas) |
| author_facet | Schromm, A.B. (Andra B.) Paulowski, L. (Laura) Kaconis, Y. (Yani) Kopp, F. (Franziska) Koistinen, M. (Max) Donoghue, A. (Annemarie) Keese, S. (Susanne) Nehls, C. (Christian) Wernecke, J. (Julia) Garidel, P. (Patrick) Sevcsik, E. (Eva) Lohner, K. (Karl) Sánchez-Gómez, S. (Susana) Martinez-de-Tejada, G. (Guillermo) Brandenburg, K. (Klaus) Brameshuber, M. (Mario) Schütz, G.J. (Gerhard J.) Andrä, J. (Jörg) Gutsmann, T. (Thomas) |
| author_sort | Schromm, A.B. (Andra B.) |
| collection | DSpace |
| description | Antimicrobial peptides (AMPs) contribute to an effective protection against infections. The antibacterial function of AMPs depends on their interactions with microbial membranes and lipids, such as lipopolysaccharide (LPS; endotoxin). Hyperinflammation induced by endotoxin is a key factor in bacterial sepsis and many other human diseases. Here, we provide a comprehensive profile of peptide-mediated LPS neutralization by systematic analysis of the effects of a set of AMPs and the peptide antibiotic polymyxin B (PMB) on the physicochemistry of endotoxin, macrophage activation, and lethality in mice. Mechanistic studies revealed that the host defense peptide LL-32 and PMB each reduce LPS-mediated activation also via a direct interaction of the peptides with the host cell. As a biophysical basis, we demonstrate modifications of the structure of cholesterol-rich membrane domains and the association of glycosylphosphatidylinositol (GPI)-anchored proteins. Our discovery of a host cell-directed mechanism of immune control contributes an important aspect in the development and therapeutic use of AMPs. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-68498 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2024 |
| publisher | PNAS |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-684982024-01-23T13:56:07Z Cathelicidin and PMB neutralize endotoxins by multifactorial mechanisms including LPS interaction and targeting of host cell membranes Schromm, A.B. (Andra B.) Paulowski, L. (Laura) Kaconis, Y. (Yani) Kopp, F. (Franziska) Koistinen, M. (Max) Donoghue, A. (Annemarie) Keese, S. (Susanne) Nehls, C. (Christian) Wernecke, J. (Julia) Garidel, P. (Patrick) Sevcsik, E. (Eva) Lohner, K. (Karl) Sánchez-Gómez, S. (Susana) Martinez-de-Tejada, G. (Guillermo) Brandenburg, K. (Klaus) Brameshuber, M. (Mario) Schütz, G.J. (Gerhard J.) Andrä, J. (Jörg) Gutsmann, T. (Thomas) Antimicrobial peptides Endotoxin Hyperinflammation Immune regulation Membrane domains Antimicrobial peptides (AMPs) contribute to an effective protection against infections. The antibacterial function of AMPs depends on their interactions with microbial membranes and lipids, such as lipopolysaccharide (LPS; endotoxin). Hyperinflammation induced by endotoxin is a key factor in bacterial sepsis and many other human diseases. Here, we provide a comprehensive profile of peptide-mediated LPS neutralization by systematic analysis of the effects of a set of AMPs and the peptide antibiotic polymyxin B (PMB) on the physicochemistry of endotoxin, macrophage activation, and lethality in mice. Mechanistic studies revealed that the host defense peptide LL-32 and PMB each reduce LPS-mediated activation also via a direct interaction of the peptides with the host cell. As a biophysical basis, we demonstrate modifications of the structure of cholesterol-rich membrane domains and the association of glycosylphosphatidylinositol (GPI)-anchored proteins. Our discovery of a host cell-directed mechanism of immune control contributes an important aspect in the development and therapeutic use of AMPs. 2024-01-23T13:56:07Z 2024-01-23T13:56:07Z 2021 info:eu-repo/semantics/article https://hdl.handle.net/10171/68498 eng info:eu-repo/semantics/openAccess application/pdf PNAS |
| spellingShingle | Antimicrobial peptides Endotoxin Hyperinflammation Immune regulation Membrane domains Schromm, A.B. (Andra B.) Paulowski, L. (Laura) Kaconis, Y. (Yani) Kopp, F. (Franziska) Koistinen, M. (Max) Donoghue, A. (Annemarie) Keese, S. (Susanne) Nehls, C. (Christian) Wernecke, J. (Julia) Garidel, P. (Patrick) Sevcsik, E. (Eva) Lohner, K. (Karl) Sánchez-Gómez, S. (Susana) Martinez-de-Tejada, G. (Guillermo) Brandenburg, K. (Klaus) Brameshuber, M. (Mario) Schütz, G.J. (Gerhard J.) Andrä, J. (Jörg) Gutsmann, T. (Thomas) Cathelicidin and PMB neutralize endotoxins by multifactorial mechanisms including LPS interaction and targeting of host cell membranes |
| title | Cathelicidin and PMB neutralize endotoxins by multifactorial mechanisms including LPS interaction and targeting of host cell membranes |
| title_full | Cathelicidin and PMB neutralize endotoxins by multifactorial mechanisms including LPS interaction and targeting of host cell membranes |
| title_fullStr | Cathelicidin and PMB neutralize endotoxins by multifactorial mechanisms including LPS interaction and targeting of host cell membranes |
| title_full_unstemmed | Cathelicidin and PMB neutralize endotoxins by multifactorial mechanisms including LPS interaction and targeting of host cell membranes |
| title_short | Cathelicidin and PMB neutralize endotoxins by multifactorial mechanisms including LPS interaction and targeting of host cell membranes |
| title_sort | cathelicidin and pmb neutralize endotoxins by multifactorial mechanisms including lps interaction and targeting of host cell membranes |
| topic | Antimicrobial peptides Endotoxin Hyperinflammation Immune regulation Membrane domains |
| url | https://hdl.handle.net/10171/68498 |
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