The role of full-length apoE in clearance of Gram-negative bacteria and their endotoxins

Ganna Petruk, Malin Elvén, Erik Hartman, Mina Davoudi, Artur Schmidtchen, Manoj Puthia, Jitka Petrlova

Research output: Contribution to journalArticlepeer-review

Abstract

ApoE is a well-known lipid-binding protein that plays a main role in the metabolism and transport of lipids. More recently, apoE-derived peptides have been shown to exert antimicrobial effects. Here, we investigated the antibacterial activity of apoE using in vitro assays, advanced imaging techniques, and in vivo mouse models. The formation of macromolecular complexes of apoE and endotoxins from Gram-negative bacteria was explored using gel shift assays, transmission electron microscopy, and CD spectroscopy followed by calculation of the α-helical content. The binding affinity of apoE to endotoxins was also confirmed by fluorescent spectroscopy detecting the quenching and shifting of tryptophan intrinsic fluorescence. We showed that apoE exhibits antibacterial activity particularly against Gram-negative bacteria such as Pseudomonas aeruginosa and Escherichia coli. ApoE protein folding was affected by binding of bacterial endotoxin components such as lipopolysaccharide (LPS) and lipid A, yielding similar increases in the apoE α-helical content. Moreover, high-molecular-weight complexes of apoE were formed in the presence of LPS, but not to the same extent as with lipid A. Together, our results demonstrate the ability of apoE to kill Gram-negative bacteria, interact with their endotoxins, which leads to the structural changes in apoE and the formation of aggregate-like complexes.

Original languageEnglish
Article number100086
JournalJournal of Lipid Research
Volume62
DOIs
Publication statusPublished - 2021 Jan 1

Subject classification (UKÄ)

  • Biochemistry and Molecular Biology

Keywords

  • Aggregation
  • Antimicrobial peptides
  • Bacteria
  • CD
  • Host defense
  • Infection
  • Innate immunity
  • Lipid A
  • Lipopolysaccharide

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