Biophysical analysis of the interaction of granulysin-derived peptides with enterobacterial endotoxins

Xi Chen, Jörg Howe, Jörg Andrä, Manfred Rössle, Walter Richter, Ana Paula Galvão da Silva, Alan M. Krensky, Carol Clayberger, Klaus Brandenburg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

To combat infections by Gram-negative bacteria, it is not only necessary to kill the bacteria but also to neutralize pathogenicity factors such as endotoxin (lipopolysaccharide, LPS). The development of antimicrobial peptides based on mammalian endotoxin-binding proteins is a promising tool in the fight against bacterial infections, and septic shock syndrome. Here, synthetic peptides derived from granulysin (Gra-pep) were investigated in microbiological and biophysical assays to understand their interaction with LPS. We analyzed the influence of the binding of Gra-pep on (1) the acyl chain melting of the hydrophobic moiety of LPS, lipid A, by Fourier-transform spectroscopy, (2) the aggregate structure of LPS by small-angle X-ray scattering and cryo-transmission electron microscopy, and 3) the enthalpy change by isothermal titration calorimetry. In addition, the influence of Gra-pep on the incorporation of LPS and LPS-LBP (lipopolysaccharide-binding protein) complexes into negatively charged liposomes was monitored. Our findings demonstrate a characteristic change in the aggregate structure of LPS into multilamellar stacks in the presence of Gra-pep, but little or no change of acyl chain fluidity. Neutralization of LPS by Gra-pep is not due to a scavenging effect in solution, but rather proceeds after incorporation into target membranes, suggesting a requisite membrane-bound step.

Original languageEnglish (US)
Pages (from-to)2421-2431
Number of pages11
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1768
Issue number10
DOIs
StatePublished - Oct 2007

Keywords

  • Antimicrobial peptide
  • Endotoxin
  • Granulysin
  • Lipopolysaccharide
  • Sepsis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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