The antimicrobial peptide cathelicidin and polymyxin B neutralize endotoxins by a multifactorial mechanism including not only direct LPS-interaction but also targeting of host cell membrane domains
Keywords: 
Antimicrobial peptides
Endotoxin
Hyperinflammation
Immune regulation
Membrane domains
Issue Date: 
2021
Publisher: 
PNAS
ISSN: 
1091-6490
Citation: 
Schromm, A.B. (Andra B.); Paulowski, L. (Laura); Kaconis, Y. (Yani); et al. "The antimicrobial peptide cathelicidin and polymyxin B neutralize endotoxins by a multifactorial mechanism including not only direct LPS-interaction but also targeting of host cell membrane domains". Biophysics and Computational Biology. 118 (17), 2021, e2101721118
Abstract
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.

Files in This Item:
Thumbnail
File
Schromm et al., 2021.pdf
Description
Size
1.56 MB
Format
Adobe PDF


Statistics and impact

Items in Dadun are protected by copyright, with all rights reserved, unless otherwise indicated.